贝伐珠单抗注射液对食蟹猴皮肤伤口愈合的影响

doi:10.12300/j.issn.1674-5817.2022.128

实验动物与比较医学 ›› 2023, Vol. 43 ›› Issue (1): 21-29.DOI: 10.12300/j.issn.1674-5817.2022.128

• 人类疾病动物模型：药学专题 • 上一篇下一篇

贝伐珠单抗注射液对食蟹猴皮肤伤口愈合的影响

杨平¹, 崔立¹()(), 俞诚², 温智越¹

^1.上海交通大学农业与生物学院, 上海 201209
^2.澎立生物医药技术(上海)股份有限公司, 上海 201203

收稿日期:2022-08-17 修回日期:2022-10-30 出版日期:2023-02-25 发布日期:2023-02-25
通讯作者: 崔立（1971—），女，博士，研究员，研究方向：人兽共患病与比较医学。E-mail： lcui@sjtu.edu.cn。ORCID： 0000-0001-5202-9671；
作者简介:杨平（1986—），男，硕士研究生，执业兽医师，研究方向：临床前药物药理药效评价。E-mail：pingyang@sjtu.edu.cn
基金资助:
上海市科委科技计划项目-实验动物专项“基于肠类器官3D培养和高内涵成像的药物毒性和安全性评价模型研究”(21140901400)

Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys

Ping YANG¹, Li CUI¹()(), Cheng YU², Zhiyue WEN¹

^1.Shanghai Jiao Tong University School Of Agriculture And Biology, Shanghai 201209, China
^2.PharmaLegacy Laboratories (Shanghai) Co. , Ltd. , Shanghai 201203, China

Received:2022-08-17 Revised:2022-10-30 Published:2023-02-25 Online:2023-02-25
Correspondence to: CUI Li (ORCID: 0000-0001-5202-9671), E-mail: lcui@sjtu.edu.cn

摘要/Abstract

摘要：

目的通过观察贝伐珠单抗注射液对食蟹猴背部皮肤伤口愈合速度及损伤皮肤组织中CD34表达的影响，验证贝伐珠单抗注射液对食蟹猴伤口愈合的延迟作用，为临床肿瘤手术患者使用贝伐珠单抗治疗时提供剂量和频次的用药参考。方法 6只雄性食蟹猴采用背部全层皮肤切除术建立伤口愈合评估模型，随机选取3只食蟹猴作为生理盐水组，其余3只食蟹猴为贝伐珠单抗组。贝伐珠单抗组食蟹猴在手术后第0、4、8、11天静脉注射30 mg/kg 贝伐珠单抗注射液，生理盐水组静脉注射等量生理盐水；术后进行血常规检测，并观察各组食蟹猴的伤口愈合情况，Image J软件分析伤口愈合率，用评分法对伤口状态的严重程度进行评价。4周后对6只食蟹猴伤口愈合皮肤取材，通过免疫组织化学法检查皮肤组织中CD34的表达水平。结果成功构建食蟹猴伤口愈合评估模型。术后第3天的食蟹猴血液中白细胞、中性粒细胞数量明显升高（P<0.05），第7天后白细胞数量逐渐恢复正常，而红细胞、血红蛋白、红细胞压积没有明显变化，提示动物营养状态良好。与生理盐水组相比，贝伐珠单抗组的伤口愈合率在术后7 d、28 d明显降低（P<0.01，P<0.001），愈合皮肤组织中CD34表达水平明显降低（P<0.01）。结论贝伐珠单抗注射给药可能通过抑制食蟹猴伤口新生皮肤组织中的微血管生成，延缓伤口愈合。临床中患者手术后使用贝伐珠单抗注射液时应该权衡利弊，科学合理地选择干预时间点、剂量、频次。

关键词: 贝伐珠单抗注射液, 伤口愈合, 伤口评分, CD34, 食蟹猴

Abstract:

Objective By observing the impact of Bevacizumab injection on the speed of wound healing and the expression of CD34 in cynomolgus monkeys, to verify its delayed wound healing mechanism, and to provide clinical reference for the dosage and frequency of Bevacizumab treatment for oncology surgery patients. Methods Six male cynomolgus monkeys underwent full-thickness skin resection on the back to establish a wound healing evaluation model. Three cynomolgus monkeys were randomly selected as the saline group, and the other three cynomolgus monkeys were allocated to the Bevacizumab treatment group. The monkeys of Bevacizumab group were administrated with Bevacizumab injection (30 mg/kg, i.v.) on day 0, day 4, day 8, and day 11, respectively. The monkeys of saline group were injected with the same volume of saline as the group receiving Bevacizumab. The blood routine test was conducted, and the wound healing of each group of cynomolgus monkeys was observed 28 days after operation. The wound healing rate was analyzed by software Image J, and the severity of the wound was assessed by scoring method. Wound healing skin samples of 6 cynomolgus monkeys were obtained after 4 weeks, and the expression level of CD34 in the wound skin tissues was detected using immunohistochemistry. Results A skin excision wound model has already been established in cynomolgus monkeys. The number of white blood cells and neutrophils in the blood of cynomolgus monkeys increased significantly on the 3^rd day after operation (P<0.05), and the number of white blood cells gradually returned to normal on the 7^th day, while the number of red blood cells, hemoglobin and hematocrit did not change significantly, suggesting that the animals were in good nutritional status. The Bevacizumab injection group wound healing rate was significantly slower than that of the saline group on day 7, and day 28^{(P<0.01, P<0.001). Microvessel density in the wound skin of Bevacizumab group appeared to be significantly lower than that of the saline group (P<0.01). Conclusion The injection of Bevacizumab may delay the wound healing by inhibiting the angiogenesis in the new skin tissue of the cynomolgus monkey. In clinical practice, the timing of giving a tumor patient a bevacizumab injection after surgery should be based on the pros and cons, and the duration, dosage, and frequency of the intervention should be chosen in a rational way.}

Key words: Bevacizumab injection, Wound healing, Wound score, CD34, Cynomolgus monkey

中图分类号:

Q95-33

杨平,崔立,俞诚,等. 贝伐珠单抗注射液对食蟹猴皮肤伤口愈合的影响[J]. 实验动物与比较医学, 2023, 43(1): 21-29. DOI: 10.12300/j.issn.1674-5817.2022.128.

Ping YANG,Li CUI,Cheng YU,et al. Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys[J]. Laboratory Animal and Comparative Medicine, 2023, 43(1): 21-29. DOI: 10.12300/j.issn.1674-5817.2022.128.

图/表 5

参考文献 30

1	GUAN Z Z, XU J M, LUO R C, et al. Efficacy and safety of Bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phaseⅢ ARTIST trial[J]. Chin J Cancer, 2011, 30(10):682-689. DOI:10.5732/cjc.011.10188 .
2	NARITA Y. Bevacizumab for glioblastoma[J]. Ther Clin Risk Manag, 2015:1759. DOI:10.2147/tcrm.s58289 .
3	MAK D Y, TJONG M C, LOUIE A V. Usage of radiotherapy with osimertinib plus Bevacizumab versus osimertinib for untreated patients with nonsquamous NSCLC Harboring EGFR mutations[J]. J Thoracic Oncol, 2023, 18(1): e3-e4. DOI:https://doi.org/10.1016/j.jtho.2022.10.010 .
4	寿建忠, 马建辉. 肾癌的靶向治疗现状与进展[J]. 中国新药杂志, 2010, 19(17):1539-1546.
	SHOU J Z, MA J H. Current status and advances in targeted therapy for renal cell carcinoma[J]. Chin J New Drugs, 2010, 19(17):1539-1546.
5	唐欣颖, 匡泽民. «接受贝伐珠单抗治疗的卵巢癌和宫颈癌患者血压管理专家共识»: 2019英国专家建议解读[J]. 中国合理用药探索, 2020, 17(1):11-15.
	TANG X Y, KUANG Z M. Interpretation of 2019 UK expert recommendations on the management of hypertension in patients with ovarian and cervical cancer receiving Bevacizumab[J]. Chin J Ration Drug Use, 2020, 17(1):11-15.
6	ZHANG H, HUANG Z, ZOU X, et al. Bevacizumab and wound-healing complications: A systematic review and meta-analysis of randomized controlled trials[J]. Oncotarget, 2016, 7(50): 82473-82481. DOI: 10.18632/oncotarget.12666 .
7	PRZEKORA A. A concise review on tissue engineered artificial skin grafts for chronic wound treatment: can we reconstruct functional skin tissue in vitro?[J]. Cells, 2020, 9(7):1622. DOI:10.3390/cells9071622 .
8	LAURENS N, KOOLWIJK P, DE MAAT M P M. Fibrin structure and wound healing[J]. J Thromb Haemost, 2006, 4(5):932-939. DOI:10.1111/j.1538-7836.2006.01861.x .
9	DE OLIVEIRA R C, WILSON S E. Fibrocytes, wound healing, and corneal fibrosis[J]. Invest Ophthalmol Vis Sci, 2020, 61(2):28. DOI:10.1167/iovs.61.2.28 .
10	URCIUOLO F, CASALE C, IMPARATO G, et al. Bioengineered skin substitutes: the role of extracellular matrix and vascularization in the healing of deep wounds[J]. J Clin Med, 2019, 8(12): E2083. DOI:10.3390/jcm8122083 .
11	VIG K, CHAUDHARI A, TRIPATHI S, et al. Advances in skin regeneration using tissue engineering[J]. Int J Mol Sci, 2017, 18(4): E789. DOI:10.3390/ijms18040789 .
12	HUGHES M R, CANALS HERNAEZ D, CAIT J, et al. A sticky wicket: defining molecular functions for CD34 in hematopoietic cells[J]. Exp Hematol, 2020, 86:1-14. DOI:10.1016/j.exphem.2020.05.004 .
13	KORNTNER S, LEHNER C, GEHWOLF R, et al. Limiting angiogenesis to modulate scar formation[J]. Adv Drug Deliv Rev, 2019, 146:170-189. DOI:10.1016/j.addr.2018.02.010 .
14	SAMI D G, HEIBA H H, ABDELLATIF A. Wound healing models: a systematic review of animal and non-animal models[J]. Wound Med, 2019, 24(1):8-17. DOI: 10.1016/j.wndm.2018.12.001 .
15	BYUN H S, LEE S J, LEE J I, et al. Effects of chitosan on wound healing in monkeys[J]. J Vet Clin, 2013, 30(4):241-246.
16	中国药品评审中心. GPT1-1: 治疗用生物制品非临床安全性技术审评一般原则 [S]. 2007.
	China Drug Review Center, GPT1-1: Guidelines for the non-clinical safety evaluation of therapeutic biological products [S]. 2007.
17	李劲锋, 于佳玥, 戴小宇, 等. 贝伐珠单抗类似药SMMU-13对食蟹猴的毒性[J]. 上海交通大学学报(农业科学版), 2018, 36(1):76-80. DOI:10.3969/J.ISSN.1671-9964.2018.01.013 .
	LI J F, YU J Y, DAI X Y, et al. Toxicitystudy of SMMU-13, a biosimilar of Bevacizumab, in cynomolgus monkeys[J]. J Shanghai Jiao Tong Univ Agric Sci, 2018, 36(1):76-80. DOI:10.3969/J.ISSN.1671-9964.2018.01.013 .
18	JIA Y, ZHAO G, JIA J. Preliminary evaluation: The effects of Aloe ferox Miller and Aloe arborescens Miller on wound healing[J]. J Ethnopharmacol, 2008, 120(2):181-189. DOI: 10.1016/j.jep.2008.08.008 .
19	APTE R S, CHEN D S, FERRARA N. VEGF in signaling and disease: Beyond discovery and development [J]. Cell, 2019, 176(6): 1248-1264. DOI:10.1016/j.cell.2019.01.021 .
20	GOLAS A R, BOYKO T, SCHWARTZ T H, et al. Prophylactic plastic surgery closure of neurosurgical scalp incisions reduces the incidence of wound complications in previously-operated patients treated with Bevacizumab (Avastin®) and radiation[J]. J Neurooncol, 2014, 119(2):327-331. DOI: 10.1007/s11060-014-1482-6 .
21	RIOS J E S, ALMEIDA F M, LIMONGI R M, et al. The effect of Bevacizumab, 5-fluorouracil, and triamcinolone on the healing modulation of surgical wounds in rats[J]. Histol Histopathol, 2023: 18583. DOI:10.14670/HH-18-583 .
22	ALMADANI Y H, VORSTENBOSCH J, DAVISON P G, et al. Wound healing: A comprehensive review[J]. Seminars in plastic surgery,2021, 35(3):141-144. DOI:10.1055/s-0041-1731791 .
23	黄丽霞, 刘基华, 刘雪莹, 等. 贝伐珠单抗生物类似药与原研药疗效及不良反应的回顾性分析比较[J]. 中国处方药, 2022, 20(8):1-4. DOI: 10.3969/j.issn.1671-945X.2022.08.002 .
	HUANG L X, LIU J H, LIU X Y, et al. Comparison of efficacy and adverse reactions between Bevacizumab biosimilar and the reference listed drug[J]. J China Prescr Drug, 2022, 20(8):1-4. DOI: 10.3969/j.issn.1671-945X.2022.08.002 .
24	RECK M, WEHLER T, ORLANDI F, et al. Safety and patient-reported outcomes of atezolizumab plus chemotherapy with or without Bevacizumab versus Bevacizumab plus chemotherapy in non-small-cell lung cancer[J]. J Clin Oncol, 2020, 38(22):2530-2542. DOI:10.1200/jco.19.03158 .
25	FINN R S, QIN S, IKEDA M, et al. Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma[J]. N Engl J Med, 2020, 382(20):1894-1905. DOI:10.1056/nejmoa1915745 .
26	AHN J W, SHALABI D, CORREA-SELM L M, et al. Impaired wound healing secondary to Bevacizumab[J]. Int Wound J, 2019, 16(4):1009-1012. DOI:10.1111/iwj.13139 .
27	冯芬, 胡斌, 招丽蓉, 等. 血清VEGF水平与贝伐珠单抗联合化疗治疗转移性结直肠癌患者疗效的关系研究[J]. 现代生物医学进展, 2017, 17(31):6136-6139. DOI:10.13241/j.cnki.pmb.2017.31.032.FENG F ,
	HU B, ZHAO L R, et al. Metastasis colorectal cancer: effects of serum VEGF and bevacizumab combined with chemotherapy[J]. Prog Mod Biomed, 2017, 17(31):6136-6139. DOI: 10.13241/j.cnki.pmb.2017.31.032 .
28	张万虎, 何亚茹, 宋瑜, 等. 康柏西普与贝伐单抗玻璃体腔注射治疗新生血管性老年性黄斑变性疗效对比观察[J]. 当代医学, 2018, 24(8):12-15. DOI:10.3969/j.issn.1009-4393.2018.08.004 .
	ZHANG W H, HE Y R, SONG Y, et al. Efficacy of conbercept versus Bevacizumab in intramuscular injection for neovascular age-related macular degeneration[J]. Contemp Med, 2018, 24(8):12-15. DOI: 10.3969/j.issn.1009-4393.2018.08.004 .
29	SIMONDS J, MILLER F, MANDEL J, et al. The effect of Bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia[J]. Laryngoscope, 2009, 119(5):988-992. DOI:10.1002/lary.20159 .
30	KWAK D H, BAE T H, KIM W S, et al. Anti-vascular endothelial growth factor (Bevacizumab) therapy reduces hypertrophic scar formation in a rabbit ear wounding model[J]. Arch Plast Surg, 2016, 43(6):491-497. DOI:10.5999/aps.2016.43.6.491 .

项目 Item	得分Score	描述 Description
伤口周围的皮肤颜色（距离伤口2 cm） Skin color around the wound (2 cm from the wound)	0	正常颜色或粉红色
	1	淡红色或有压之褪色的发红
	2	白色或灰白色
	3	深红色或压之不褪色的发红
	4	黑色或色素沉着过度
伤口周围组织水肿 Edema in wound surrounding tissue	0	无水肿或肿胀
	1	伤口周围非凹陷水肿范围<2 cm
	2	伤口周围非凹陷水肿范围≥2 cm
	3	伤口周围凹陷水肿范围<2 cm
	4	伤口周围凹陷水肿范围≥2 cm
渗出液类型 Type of exudate	0	无渗出液
	1	红色
	2	粉红色
	3	薄而透明，水性
	4	黄色或绿色，气味难闻
渗出量 Exudate amount	0	无渗出液
	1	伤口组织微湿，但无法测量
	2	伤口组织湿润，浸泡<25%的敷料
	3	伤口组织湿润，浸泡敷料的25%～75%
	4	伤口组织湿润，浸泡>75%的敷料

项目 Item	得分Score	描述 Description
伤口周围的皮肤颜色（距离伤口2 cm） Skin color around the wound (2 cm from the wound)	0	正常颜色或粉红色
	1	淡红色或有压之褪色的发红
	2	白色或灰白色
	3	深红色或压之不褪色的发红
	4	黑色或色素沉着过度
伤口周围组织水肿 Edema in wound surrounding tissue	0	无水肿或肿胀
	1	伤口周围非凹陷水肿范围<2 cm
	2	伤口周围非凹陷水肿范围≥2 cm
	3	伤口周围凹陷水肿范围<2 cm
	4	伤口周围凹陷水肿范围≥2 cm
渗出液类型 Type of exudate	0	无渗出液
	1	红色
	2	粉红色
	3	薄而透明，水性
	4	黄色或绿色，气味难闻
渗出量 Exudate amount	0	无渗出液
	1	伤口组织微湿，但无法测量
	2	伤口组织湿润，浸泡<25%的敷料
	3	伤口组织湿润，浸泡敷料的25%～75%
	4	伤口组织湿润，浸泡>75%的敷料

指标及组别 Index and group	手术后时间 Time after surgery/d
指标及组别 Index and group	0	3	7	14	28
WBC/(10⁹·L^-1)
生理盐水组 Saline group	13.20±0.08	31.00±1.05^△	14.65±0.10	15.64±0.08	18.70±0.69
贝伐珠单抗组 Bevacizumab group	12.15±0.09	25.25±0.08^△	13.48±0.04	15.72±0.50	17.14±0.23
RBC/(10¹²·L^-1)
生理盐水组 Saline group	5.80±0.21	6.01±0.48	6.22±0.13	5.88±0.35	5.99±0.34
贝伐珠单抗组Bevacizumab group	6.10±0.16	5.84±0.43	5.97±0.15	5.72±0.11	5.84±0.18
NEU/%
生理盐水组 Saline group	44.03±2.23	81.80±3.98^△	50.97±4.83	61.57±6.75	60.73±17.91
贝伐珠单抗组 Bevacizumab group	59.67±4.58	66.50±10.38	61.6±4.85	58.57±7.83	74.40±4.97
NEU/(10⁹·L^-1)
生理盐水组 Saline group	5.81±0.30	25.41±1.93^△△	7.46±0.66	9.61±1.01	11.53±3.54
贝伐珠单抗组 Bevacizumab group	7.26±0.59	16.80±2.62^△	8.31±0.66	9.25±1.39	12.74±0.83
LYM/%
生理盐水组 Saline group	50.37±2.92	14.53±3.75	43.17±3.76	30.97±6.64	30.37±14.77
贝伐珠单抗组 Bevacizumab group	33.30±4.35	28.43±9.75^*△	33.93±5.04	34.53±7.23	20.30±4.66
LYM/(10⁹·L^-1)
生理盐水组 Saline group	6.65±0.38	4.44±1.08	6.33±0.59	4.86±1.06	5.52±2.52
贝伐珠单抗组 Bevacizumab group	4.05±0.52	7.18±2.48	4.58±0.68	5.40±1.05	3.48±0.78
HG1B ρ/(g·L^-1)
生理盐水组 Saline group	140.00±3.06	147.00±7.00	149.33±5.84	144.33±7.17	139.00±3.61
贝伐珠单抗组 Bevacizumab group	150.00±5.57	142.33±7.06	142.67±7.84	140.67±2.73	140.33±3.84
HCT/%
生理盐水组 Saline group	45.93±1.13	47.27±2.20	47.93±2.15	45.73±2.22	44.97±1.90
贝伐珠单抗组 Bevacizumab group	48.70±1.65	45.40±2.39	45.93±2.05	45.87±1.22	45.30±1.56
EOS/%
生理盐水组 Saline group	0.87±0.29	0.43±0.34	1.23±0.29	2.13±0.95	3.50±3.06
贝伐珠单抗组Bevacizumab group	0.83±0.38	0.47±0.20	0.27±0.03	1.57±0.75	0.73±0.35
EOS/(10⁹·L^-1)
生理盐水组 Saline group	0.12±0.04	0.14±0.10	0.18±0.04	0.33±0.15	0.62±0.54
贝伐珠单抗组 Bevacizumab group	0.10±0.05	0.11±0.05	0.03±0.01	0.24±0.11	0.13±0.06

指标及组别 Index and group	手术后时间 Time after surgery/d
指标及组别 Index and group	0	3	7	14	28
WBC/(10⁹·L^-1)
生理盐水组 Saline group	13.20±0.08	31.00±1.05^△	14.65±0.10	15.64±0.08	18.70±0.69
贝伐珠单抗组 Bevacizumab group	12.15±0.09	25.25±0.08^△	13.48±0.04	15.72±0.50	17.14±0.23
RBC/(10¹²·L^-1)
生理盐水组 Saline group	5.80±0.21	6.01±0.48	6.22±0.13	5.88±0.35	5.99±0.34
贝伐珠单抗组Bevacizumab group	6.10±0.16	5.84±0.43	5.97±0.15	5.72±0.11	5.84±0.18
NEU/%
生理盐水组 Saline group	44.03±2.23	81.80±3.98^△	50.97±4.83	61.57±6.75	60.73±17.91
贝伐珠单抗组 Bevacizumab group	59.67±4.58	66.50±10.38	61.6±4.85	58.57±7.83	74.40±4.97
NEU/(10⁹·L^-1)
生理盐水组 Saline group	5.81±0.30	25.41±1.93^△△	7.46±0.66	9.61±1.01	11.53±3.54
贝伐珠单抗组 Bevacizumab group	7.26±0.59	16.80±2.62^△	8.31±0.66	9.25±1.39	12.74±0.83
LYM/%
生理盐水组 Saline group	50.37±2.92	14.53±3.75	43.17±3.76	30.97±6.64	30.37±14.77
贝伐珠单抗组 Bevacizumab group	33.30±4.35	28.43±9.75^*△	33.93±5.04	34.53±7.23	20.30±4.66
LYM/(10⁹·L^-1)
生理盐水组 Saline group	6.65±0.38	4.44±1.08	6.33±0.59	4.86±1.06	5.52±2.52
贝伐珠单抗组 Bevacizumab group	4.05±0.52	7.18±2.48	4.58±0.68	5.40±1.05	3.48±0.78
HG1B ρ/(g·L^-1)
生理盐水组 Saline group	140.00±3.06	147.00±7.00	149.33±5.84	144.33±7.17	139.00±3.61
贝伐珠单抗组 Bevacizumab group	150.00±5.57	142.33±7.06	142.67±7.84	140.67±2.73	140.33±3.84
HCT/%
生理盐水组 Saline group	45.93±1.13	47.27±2.20	47.93±2.15	45.73±2.22	44.97±1.90
贝伐珠单抗组 Bevacizumab group	48.70±1.65	45.40±2.39	45.93±2.05	45.87±1.22	45.30±1.56
EOS/%
生理盐水组 Saline group	0.87±0.29	0.43±0.34	1.23±0.29	2.13±0.95	3.50±3.06
贝伐珠单抗组Bevacizumab group	0.83±0.38	0.47±0.20	0.27±0.03	1.57±0.75	0.73±0.35
EOS/(10⁹·L^-1)
生理盐水组 Saline group	0.12±0.04	0.14±0.10	0.18±0.04	0.33±0.15	0.62±0.54
贝伐珠单抗组 Bevacizumab group	0.10±0.05	0.11±0.05	0.03±0.01	0.24±0.11	0.13±0.06

[1]	李鹤龄, 钱子瑶, 覃刚民, 蒋德兵, 张艳琼, 金文政, 王宏. 食蟹猴源弗氏柠檬酸杆菌的分离鉴定及生物学特性分析[J]. 实验动物与比较医学, 2026, 46(3): 367-377.
[2]	王晨娟, 杨玲焰, 王立鹏, 孙雪萍, 李静文, 郭连香, 荣荣, 时长军. 2019年某实验猴养殖场食蟹猴犬瘟热暴发的诊断[J]. 实验动物与比较医学, 2025, 45(3): 360-367.
[3]	韦炎冶, 申果, 张鹏飞, 石松平, 胡家豪, 张绪哲, 花慧源, 花冠洋, 陆宏正, 曾勇, 季风, 韦祝梅. 肥胖食蟹猴一般身体指标、血糖、血脂的动态监测及相关性分析[J]. 实验动物与比较医学, 2025, 45(1): 30-36.
[4]	卞新彦, 陆勇, 王燕, 孙强. 食蟹猴分娩行为分析[J]. 实验动物与比较医学, 2023, 43(4): 355-362.
[5]	韦祝梅, 申果, 李振明, 曾勇, 季风, 杨继红. 不同年龄段食蟹猴骨矿含量与骨密度测定分析[J]. 实验动物与比较医学, 2022, 42(5): 409-415.
[6]	高仕平, 李锋, 查思凡. 高脂饮食诱导的非酒精性脂肪肝病食蟹猴模型[J]. 实验动物与比较医学, 2020, 40(2): 123-127.
[7]	王成舟. 食蟹猴急性心肌梗死模型的建立及护理[J]. 实验动物与比较医学, 2019, 39(4): 314-318.
[8]	李良顺, 潘世友, 支元芳, 白帅州, 孙建华, 宫丽崑, 任进. 一例食蟹猴肠套叠诊断与治疗[J]. 实验动物与比较医学, 2019, 39(3): 236-238.
[9]	韦毅, 符明泰, 阳明, 黄卫宣, 蓝娇, 覃喜军, 玉宁. 正常成年雄性食蟹猴部分免疫功能指标观测[J]. 实验动物与比较医学, 2018, 38(3): 236-238.
[10]	李伟, 金益, 邢正弘, 陈国强. 单笼与群居饲养对雌性食蟹猴情绪的影响[J]. 实验动物与比较医学, 2017, 37(1): 46-49.
[11]	李伟, 金益, 柏熊, 王晓东, 邢正弘, 王校权. 单笼与群居饲养对雌性食蟹猴生理指标的影响[J]. 实验动物与比较医学, 2016, 36(5): 369-373.
[12]	邢正弘. 湿帘降温原理及其在食蟹猴饲育设施中的初步应用[J]. 实验动物与比较医学, 2016, 36(2): 141-145.
[13]	韦祝梅, 杨波, 李振明, 韩银华, 苏科龙, 杨继红. 肥胖及糖尿病食蟹猴全天血糖、胰岛素值及相关生理指标观测[J]. 实验动物与比较医学, 2015, 35(5): 394-397.
[14]	杨波, 韦祝梅, 邓信宁, 何乃知, 李振明, 杨继红. 利用MRI检查建立食蟹猴腓肠肌体积检测方法[J]. 实验动物与比较医学, 2014, 34(4): 314-318.
[15]	多海刚, 桑传兰, 陈子亮, 梁兴林, 李比海, 金石军, 饶军华. 食蟹猴麻疹胎传抗体及其仔猴初次接种麻疹疫苗免疫效果的研究[J]. 实验动物与比较医学, 2013, 33(5): 347-350.

贝伐珠单抗注射液对食蟹猴皮肤伤口愈合的影响

Effects of Bevacizumab Injection on the Skin Wound Healing in Cynomolgus Monkeys

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 5

参考文献 30

相关文章 15

编辑推荐

Metrics

本文评价