Table of Content

25 August 2014, Volume 34 Issue 4

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Initially Establishment and Characterization of Patient Derived Gastric Cancer Xenograft Models

XU Chun-hua, YANG Lei, TANG Xu-zhen, HU Gang, GENG Qin, OU YANG Ke-dong, XIE Fu-bo, WANG Ke, QIN Xiao-ran, LIU Ji-bin, YANG Wei-min, TAO Wei-kang, ZHANG Yi-xin, ZHOU He

2014, 34(4):  259-265.  DOI: 10.3969/j.issn.1674-5817.2014.04.001

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Objective To establish the patient derived gastric cancer xenografts by subcutaneous implantation of clinical gastric cancer specimens in immunodeficient mice, and assess its characters. Methods Ninety-eight fresh human gastric cancer specimens were subcutaneously implanted into SCID mice. They were serially passaged with BALB/c-nu/nu mice when the xenograft tumors reached size 500~1000 mm³. Tumors were cryoperserved in liquid nitrogen for future model recovery, and also snap frozen, paraffin-embedded for future analysis. H&E staining and pathological analyses were also performed. Twelve selected patient derived gastric cancer xenograft models were evaluated by in vivo efficacy studies and in vitro chemo sensitivity studies. Results 25 gastric cancer xenografts successfully developed into tumor and could be continuously passaged to next generations, the engraftment efficency is 25.52%. These xenografts showed similar histological features compared with the original clinical specimen. Efficacy studies in vivo showed individual differences in sensitivity to 5-FU and cisplatin among different models: 2 xenografts were highly inhibited by 5-FU (TGI>60%), the same treatment is less effective in the other 10 xenografts; 3 xenografts were completely inhibited by cisplatin (TGI>100%), 4 xenografts were highly inhibited by cisplatin (TGI, 60%-90%), and 5 other xenografts were relatively insensitive to cisplatin treatment (TGI<60%). Chemo sensitivity studies in vitro were performed with 3 representative models, their sensitivity to 5-FU is GAX001(IC₅₀:3.187 μmol) > GAX007(IC₅₀:6.886 μmol) > GAX027(IC₅₀:8.323 μmol), and their sensitivity to cisplatin is GAX027(IC₅₀:2.753 μmol) > GAX001(IC₅₀:3.211 μmol) > GAX007(IC₅₀:8.137 μmol). Conclusions 25 Patient derived gastric cancer xenograft models were successfully established. The transplanted tumors showed similar histological features compared with the original clinical specimen. From the results of the 12 efficacy study, the xenografts showed differently sensitivity to different chemotherapy, representing different chemo-responses in the clinic. These gastric cancer models are valuable for anti-cancer drug development and research



The Research on Inflammation Marker of Prostatitis Induced by Carrageenan in Rats

ZHOU Li, LUO Yong-wei, WANG Yong, WANG Rong, JIA Yu-ling, CHEN Ying, LIU Xiang-yun, SUN Zu-yue

2014, 34(4):  266-271.  DOI: 10.3969/j.issn.1674-5817.2014.04.002

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Objective To explore the inflammation markers in prostatitis induced by carrageenan in rats. Methods Twenty rats were randomly divided into two groups, negative control group and model group (1% carrageenan), each group with 10 ones. Model group was injected with 0.1 ml 1% carrageenan physiological saline solution into the prostate. The negative control group was injected with equal dose of physiological saline at the same time and location. Results In model group, there were volume and a small amount of lymphocytes and mononuclear cells infiltration in the prostatic stroma, which showed obvious chronic inflammation. Compared with negative control group, CRP (C-reactive protein) content was significantly increased (P<0.05) in model group. The level of testosterone was significantly increased (P<0.01) and estrogen was decreased (P<0.05). Conclusion The chronic non-bacterial prostatitis can be induced by carrageenan, and lead to the changes of the inflammation markers, such as CRP, testosterone and estrogen.



Effect of Salvianolic acid A Injection on CCl₄-induced Liver Fibrosis in Rats

LU Ting, ZHU Ke-yan, CHEN Fang-ming, CAI Yue-qin, SHOU Qi-yang, PAN Yong-ming, CHEN Min-li

2014, 34(4):  272-277.  DOI: 10.3969/j.issn.1674-5817.2014.04.003

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Objective To investigate the effect of salvianolic acid A(SAA) on CCl₄-induced liver fibrosis in rats. Methods The liver fibrosis rat model was made by subcutaneous injection of CCl₄. After 4 weeks, they were divided into model control group, high and low dose SAA groups, salvianolic acid (SA) capsule group, and normal control group. High and low dose groups were intravenously injected with 5 mg/kg, 2.5 mg/kg SAA, respectively. The SA capsule group was orally administered 50 mg/kg salvianolic acid powder. Model and normal control groups were intravenously injected with 10 ml/kg Saline.The serum AST and ALT levels, liver coefficient, hydroxyproline(Hyp) content, and type I, Ⅲ collagen expression in liver tissue were detected 8 weeks later. Results Compared with control group, the symptom in high and low doses SAA group and SA capsule group rat were significantly improved, liver coefficient ,ALT and AST activities, Hyp content and type I,III collagen expression were significantly reduced in high doses SAA group (P<0.05, P<0.01). Conclusions Salvianolic acid A injection has anti-Liver fibrosis effects, and the effects with 5 mg/kg SAA injection by intravenous was superior to 50 mg/kg salvianolic acid capsule by oral administration.



Influence of Ulinastain on Serum Expression of Inflammation Cytokines in Rat with Multiple Organ Dysfunction Syndrome

FENG Xiao-ming, WANG Hong-yi, NIU Ting-xian, WAN Dong-jun, LU Lu, WANG Chun-yu, LUO Xiao-hong

2014, 34(4):  278-282.  DOI: 10.3969/j.issn.1674-5817.2014.04.004

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Objective To evaluate the protective effects of Ulinastatin (UTI) on multiple organ dysfunction syndrome (MODS) in rat by detecting serum expression of inflammation cytokines. Methods Ninety rats were randomly divided into 3 groups, the control group, model group and UTI group, model group and UTI group were infused with 15 μg / kg lipopolysaccharide(LPS) in vena caudalis, and the UTI group were intraperitoneally injected with 1×10⁵ U/kg UTI for prevention and therapy before and after the model established . Then the physical sign appearance was observed and the serum was collected to determine the expression of TNF-α、IL-1α、IL-4 and IL-10 by ELISA in each group at different time points. Results ① The mortalities were 0%, 33%, and 16% in the control, model and UTI group respectively. ② The expression concentration of TNF-α、IL-1α in UTI group were lower compared with those of model group. ③ The expression concentration of IL-4 in model group has significant increase compared with that of control group at 0 h, 12 h (P<0.05) and 24 h(P<0.01); The expression concentration of IL-10 in model group has significant increase compared with that of control group at12 h (P<0.05), UTI group has significant ascendant compared with control group at 6~12 h has significant ascendant (P<0.05). Conclusion The UTI could decrease the mortality of MODS induced by LPS, and it could reduce the increased amplitude of serum levels of TNF-α、IL-1α, whereas enhance the increased amplitude of the serum IL-4 and IL-10, it could also prevent the happen and development of MODS efficiently.

Effects of Salbutamol on Ventilator-induced Lung Injury in Aged Rats

CHEN Mei-lian, LAI Guo-xiang, LIU De-ling, ZHUO Hui-chang

2014, 34(4):  283-287.  DOI: 10.3969/j.issn.1674-5817.2014.04.005

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Objective To investigate the influence of salbutamol in aged rat model of ventilator-induced lung injury (VILI)and its underlying mechanism. Methods Twenty-four healthy male Wistar rats were randomly divided into three groups to receive different ventilation protocols for 4h: normal control group (group 1), VILI without treatment (group 2), VILI treated with salbutamol(group 3). After ventilation, the activity of SOD, XOD and the level of MDA, TNF-á, IL-2, IL-6 and IL-8 in left lung tissue were detected. Lung histopathology was assessed by HE staining and electron microscopic observation. Results After 4h mechanical ventilation, the activity of SOD and XOD in lung tissue was significantly higher in group 3 than those of group 2. The level of MDA, TNF-α, IL-2 and IL-6 in lung tissue was significantly lower in group 3 than those of group 2. Histopathologic findings demonstrated that the destruction of lung tissue in group 2 was more serious than group 3. Conclusion Salbutamol reduced the inflammatory reaction, at the same time improved the various antioxidant activity and microcirculation, thereby reduced pulmonary edema of lung tissue and played certain protective function on ventilator-induced lung injury in aged rats.



The Role of Indoleamine 2,3-dioxygenase in Candida Parapsilosis Systemic Infectet Mice

WU Yu-e, ZHANG Yu, GONG Bao-yong, CHEN Meiling, WU Rui-ke, JIA Huan-huan, LUO Ting, GAO Xiang, HUANG Ren

2014, 34(4):  288-293.  DOI: 10.3969/j.issn.1674-5817.2014.04.006

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Objective To investigate the role of indoleamine 2,3-dioxygenase (IDO) in mice model of candida parapsilosis(CP) systemic infection. Methods The female ICR mice (SPF) were randomly divided into three groups, Group A and Group B were infected with CP by tail vein injection after immunosuppression, control group were injected physiological saline by tail vein injection. Group B were given methyl tryptophan (1-MT) by oral gavage, which is the inhibitor of IDO, each a day from 0 day to 7 days after infection. While group A and control group were given physiological saline by oral gavage. Five mice were euthanatized at 3, 6, 9 days after infection and the kidney tissues were collected and examined by the expression of IDO and inflammation related cytokines, fungal burden, and histology. Results After infection CP, the level of IDO in Group A was increased, while the IDO level was went down in group B. The level of IFN-γ, NF-α, IL-6 and IL-1β in kidney was increased both in group A and group B comparing with control group. At 6 days after infection, the level of IL-17 in kidney in group B was increased significantly comparing with that of group A and control group. At 6 days after infection, the level of fungal burden in group B were higher than that of group A. More fungal infection focus and tissue destruction were seen in the kidneys under the microscope in group B. Conclusion The expression level of IDO was increased in the mice model of CP systemic infection. When the inhibitor of IDO were given to the CP mice, the level of IL-17 in kidney was increased, which might promote chronic inflammation and inhibit the clearing of fungi.



Effects of Eight Weeks Aerobic Endurance Exercise on Food Consumption, Body Composition, and Blood Lipids in Normal and Obese Rats

ZHANG Yun-li, CAI Ming, LI Jing-jing, XIN Lei, LOU Shu-jie

2014, 34(4):  294-298.  DOI: 10.3969/j.issn.1674-5817.2014.04.007

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Objective To study the differences of food consumption, body composition and blood lipids between normal-weight and obese rats during eight weeks aerobic endurance exercise. Methods Firstly, a rat model of nutritional obesity was established by feeding with a high-fat diet, and then these obese rats were randomly divided into two groups, obesity control (OC) group, and obesity exercise (OE) group.In addition, a normal control (NC) group and a normal exercise (NE) group were set up. After grouped, the exercise groups were arranged for eight weeks aerobic endurance exercise . During the experimental period, diet consumption of the rats was measured every day afternoon. After the exercise intervention , body composition of the rats was determined with Prodigy dual-energy X-ray absorptiometry, and blood lipids with the automatic biochemistry analyzer. Results 1) Diet consumptions of 1,4,7-week in NE group were significantly lower than that in NC group (P<0.05); Diet consumptions of 1,2,3,4,6,8 -week in OE group were significantly lower than that in OC group (P<0.05); 2) Compared with OC group, whole-body adipose tissue mass and body fat percentage were significantly decreased in OE group (P<0.05), but there was no significant difference between NE group and NC group (P>0.05); 3)Whole-body muscle tissue mass and muscle percentage in OE group were significantly higher than that in OC group (P<0.05), but there was no significant difference between NE group and NC group (P>0.05); 4)Whole-body bone mineral density in NE group increased, was significantly greater than that in NC group (P<0.05), but there was no significant difference between OE group and OC group (P>0.05); 5) serum TG levels in OE group were significantly lower than that in OC group (P<0.05), but there was no significant difference between NE group and NC group (P>0.05). Conclusion The same intensity aerobic endurance exercise caused different effects on food consumption, whole-body adipose tissue mass, muscle tissue mass, bone mineral density and serum TG levels between normal-weight and obese rats.

Establishment of Peritoneal Adhesion Model in Wuzhishan Minipigs

PAN Jin-chun, MIN Fan-gui, WANG Xi-long, CHEN Rui-ai, WANG Feng-guo, LUO Shu-ming

2014, 34(4):  299-302.  DOI: 10.3969/j.issn.1674-5817.2014.04.008

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Objective To establish a peritoneal adhesion model in Wuzhishan minipigs. Methods Fourteen Wuzhishan minipigs were anesthetized by Sumianxin II with intramuscular injection and pentobarbital sodium with intravenous injection after fasting overnight. Then, the abdominal cavity were opened under laparotomy. Afterwards, the peritoneal adhesion model was established by physical damage of serosal, chemical damage, vascular ligation and ligation of parietal peritoneum. Result Peritoneal adhesions were found 1 day after the operation with the degree of adhesion score 2 and adhesion area score 2~3. Peritoneal adhesions were serious 3 days after the operation with the degree of adhesion and adhesion area score 3~4. The adhesions was sustained for a long time, and peritoneal adhesions still existed 12 months after the operation with the degree of adhesion and adhesion area score 2~3. There were no obvious difference in the degree of adhesion and adhesion area between males and females. Conclusion The peritoneal adhesion model were succeesfully established in Wuzhishan minipigs by multifactors.



Effects of Chinese Propolis on Gastric Mucosa of Mongolian Gerbils Infected with Helicobacter pylori

REN Xiao-li, LIN Gang, WANG Jie-jie, DU Ji-mei

2014, 34(4):  303-307.  DOI: 10.3969/j.issn.1674-5817.2014.04.009

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Objective To investigate the effects of Chinese propolis on gastric mucosa in Helicobacter pylori (Hp) infected Mongolian gerbils. Methods Fifteen 5-week-old Mongolian gerbils were randomly divided to three groups: control group , infection group, and propolis treatment group.The first two groups were inoculated with 0.5 ml of Hp (10⁹ cfu/ml) by intragastric administration(i.g) for 3 times after 24 h fasting while control group was taken broth by i.g . 4 weeks after the first infection , i.g was repeated once every 5 days.At the 16^th week, the gerbils were inoculated with 0.5 ml of Hp (10⁹ cfu/ml) by i.g for consecutive 5 days to enhance infection. Gerbils in the propolis group were inoculated with propolis by i.g at the 22^th and 24^th week after the first infection, while the other two groups were inoculated with sterile saline in the same way. All the gerbils were sacrificed at the 27^th week. The liver, kidney and spleen were removed to measure the organ coefficient. Gastric mucosa was removed to determine the concentration of Hp and for pathological observation. Results Compared with the control, the infection group exhibited a lower serum IL-8 level (P<0.05), while the propolis group significantly elevated the serum IL-8 level compared with the infection group (P<0.01); the organ coefficient of liver, kidney and spleen were not significant among groups (P>0.05); the concentration of Hp in the propolis group (2.46±1.72 cfu/mg) was significantly lower (P<0.05) than that in the infection group (10.75±6.88×10²cfu/mg) (P<0.05); histological examination showed more serious mucosal inflammation in the the infection group. Conclusion The Propolis may inhibit the growth of Hp in the stomach of gerbils, and enhance anti-inflammatory ability in Hp-infected gerbils. Chinese propolis may play a role in mucosal repair and organ protection.

Observation on Microcirculation of Uterine Wall and Mesometrium in Rats

LIU Jian-gang, ZHANG Lei, LI Jie, ZHANG Da-wu

2014, 34(4):  308-313.  DOI: 10.3969/j.issn.1674-5817.2014.04.010

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Objective To establish observation the methods for microcirculation of uterine wall and mesometrium in rats. Methods Thirty female SD rats were anesthetized through intraperitoneal injection with 2% pentobarbital sodium(30 mg/kg). After routine abdomen disinfection, the rats were fixed in supine position, with two lower limbs abducted maximally. A longitudinal cut was made whose length was 1.5~2 cm and 0.5cm outside of abdomen midline. We made blunt dissection of subcutaneous tissue and draw one side of uterus and its ligament. Put uterus and the ligament on microcirculation calorstat which was in transparent plexiglass groove with water controlled temperature of 37.5℃. The uterus and ligament were fixed and flattened on the pillai, a small plexiglass pillar which was 20 mm width and 15 mm height ,used for observation. The tissues were kept moist with 37℃ Riger's solution. The microcirculation of uterine wall and mesometrium were observed and calculated capillary parameter value with the use of cold light source as an external light. The microcirculation of uterus of 15 rats were observed 30 min post 2 IU (international Unit) oxytocin IV injection. Results The diameter of arteriole in mesometrium of rats was 8~15 μm, while the diameter of its microvein was 25~45 μm, the diameter of arteriole of uterine wall was 6~12 μm, and while the diameter of its microvein was 15~30 μm. After the injection of oxytocin, the diameter of arteriole of mesometrium and uterine wall decreased 38.24% and 25.14% respectively, which has significantly difference comparing with normal group (P<0.05, P<0.05). Conclusion The anatomical position of mesometric capillary of rats is obvious and easy for dissection. The blood vessels of microcirculation are clear and have abundant blood flow, which are benefit for human disease prevention and medicine study.



Established Method of Measurement for Gastrocnemius Volume in Cynomolgus Monkeys by MRI Detection

YANG Bo, WEI Zhu-mei, DENG Xin-ning, HE Nai-zhi, YIN Feng-ri, LI Zhen-ming, YANG Ji-hong

2014, 34(4):  314-318.  DOI: 10.3969/j.issn.1674-5817.2014.04.011

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Objective To evaluate the measurement of the gastrocnemius voulme by MRI detection in Cynomolgus monkeys. Methods Right lower limbs of two Cynomolgus monkeys were fixed with fiber polymer bandages (from knee to ankle) for 15 weeks. By performing MRI examinations on the gastrocnemiuses of both legs at week 11, 13 and 15Ł¬257 images were obtained. After measuring the coronal area of the gastrocnemius for 3 times by the same person and different persons, the volume of gastrocnemius was determined. Areas in all images detected by the same person at different time and areas in all images detected by different persons were compared, respectively. Result The gastrocnemiuses were all clearly detected in the MRI images. The measurement error of the area of the gastrocnemius in all images by the same person was 0 ~3.47 cm². The percentage of the mean difference in the total area of one leg was 0.8%, and the CV was 1.34%. The measurement error by different persons was 0 ~3.47 cm². The percentage of the mean difference in the total area of one leg was 1.7%, and the CV was 1.08%. The measurement error by different persons at the same period was 0 ~1.5 cm³. The percentage of the mean difference in one leg volume was 5.8%, and the CV was 6.5%. Conclusion MRI examination may be used as a valuable method in evaluating the muscle atrophy model in Cynomolgus monkeys with comparatively higher accuracy and lower error by combining the manual operation and software control.



Fitting, Comparison and Analysis of Two Kinds of Growth Curve in Chinese Experimental Miniature Pig

WANG Ji-xing

2014, 34(4):  319-323.  DOI: 10.3969/j.issn.1674-5817.2014.04.012

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Objective Logistic growth model and Gompertz growth model were applied in fitting ,comparison and analysis of early growth and development of Chinese Experimental Miniature Pig(CEMP),in order to find out appropriate growth curve model. Methods The body weight of closed colony in CEMP were measured every 7 days from the age of 1~6 weeks and every 14 days from the age of 8~26 weeks, then the fitting analysis of growth and development of closed colony of breeding pigs in early stage were carried on by Logistic growth model and Gompertz growth model. Results The results of Gompertz growth model were more closed to actual situation by comparison of Logistic growth mode. By Gompertz growth model,the estimated results of our closed colony were as follows:the maximum weight was 31.13 kg, growth spinod age in days was 101.31 d, growth spinod weight was 11.45 kg. The average daily gain was increased from 0.0343 kg/d(7 days) to the maximum value of 0.1603 kg/d(101.3 days), then gradually decreased, so the growth rate increased initially and decreased afterwards. Conclusion Appropriate growth curve model of breeding and feeding for closed colony of CEMP was established in our research, which makes referential and practical importance in improving methods of feeding and management and breeding,and so on.



Spontaneous Tumorigenesis, Hematological and Serum Biochemical Parameters of Senile Wistar Rats

XIAO Cheng-rong, TAN Hong-ling, MA Zeng-chun, WANG Yu-guang, WANG De-wen, SUN Jing-xiang, GAO Yue

2014, 34(4):  324-329.  DOI: 10.3969/j.issn.1674-5817.2014.04.013

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Objective To measure spontaneous tumorigenesis, hematological, and serum biochemical parameters of Wistar rats feeding for two years. Methods Wistar rats feeding for two years were killed to determinate peripheral blood and serum biochemical parameters, and spontaneous tumorigenesis was also investigated. Results Wistar rats were raised in GLP laboratory for two years, the cancer of skin, hypodermis and adipose tissue was widespread, tumorigenesis of nervous or genital system was also observed, and tumorigenesis of digestive system was found in male rats. Compared with female rats, parameters of white blood cells (WBC), mean corpuscular volume (MCV), alkaline phosphatase (ALP), albumin (Alb), glucose (Glu), total cholesterol (CHO), creatine kinase (CK) were changed obviously in male rats. Conclusion Normal reference range of Wistar rats feeding for two years was set up in order to evaluate rodent animals carcinogenicity for new drug.



The Preliminary Analysis of Quarantine Parameters in Common Marmosets' Infectious Diseases

LI Meng-qian, WANG Qing-song, ZHANG Zhan-heng, LIU Xiao-long, WANG Xing-tong, LI Ting-ting, YIN Hai-fang, LIU Feng-yong

2014, 34(4):  330-334.  DOI: 10.3969/j.issn.1674-5817.2014.04.0014

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Objective To investigate the infectious disease for the eight common marmosets importedfrom South Africa and 10 marmosets bred by Tianjin Medical Universityto set up a preliminary standard for marmoset's infectious test by the comparing. Methods In quarantine test: the hepatitis A virus in blood, B-ultrasound for liver, tuberculin skin test for tuberculin, parasite in stool test, microorganism or pathogenic bacteria in intestinal tract and the herpes virus in the skin or mouth were detected by ELISA. Results The result of all the cases were negative. Conclusion All the marmosets are not infected; the quarantine methods used are safe, effective and suitable for the common marmoset.



Differences on Care and Use of Laboratory Animals in Research Institutions between China and USA

YU Yan, LIU Ji-hong, ZHU Feng-xian, ZHOU Yan, LU Jia-qi

2014, 34(4):  335-338.  DOI: 10.3969/j.issn.1674-5817.2014.04.015

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With the globalization of biomedical and pharmaceutical research and development, the care and use of laboratory animals in research institutions, as an important component in biomedical research, are also facing the opportunities and challenges with the globalization. In USA, the care and use of laboratory animals program, especially animal welfare, are all very advanced and high standards comparing with China. In order to find related disadvantages, further to improving the program in China research institutions, this article will focus on the analysis of differences in the care and use of laboratory animals between China and USA research institutions.