实验动物与比较医学 ›› 2024, Vol. 44 ›› Issue (2): 127-138.DOI: 10.12300/j.issn.1674-5817.2023.150
• 人类疾病动物模型 • 下一篇
钟瑞华1, 李国停1, 杨文捷1, 郭湘洁1, 周洁芸1, 胡颖怡1, 倪其承1,2, 杨野1,2, 张敏3, 朱焰1(
)(
)
收稿日期:2023-11-03
修回日期:2024-02-01
出版日期:2024-05-09
发布日期:2024-04-25
通讯作者:
朱 焰（1970—），女，博士，研究员，从事生殖药理学研究。E-mail： zhuyan@sippr.org。ORCID： 0000-0001-5136-7601作者简介:钟瑞华（1988—），女，硕士，助理研究员，从事生殖药理学研究。E-mail： zrh8804@126.com
Ruihua ZHONG1, Guoting LI1, Wenjie YANG1, Xiangjie GUO1, Jieyun ZHOU1, Yingyi HU1, Qicheng NI1,2, Ye YANG1,2, Min ZHANG3, Yan ZHU1()()
Received:2023-11-03
Revised:2024-02-01
Published:2024-04-25
Online:2024-05-09
Contact:
ZHU Yan (ORCID:0000-0001-5136-7601), E-mail: zhuyan@sippr.org摘要：
目的 用同种异体移植的方法构建大鼠子宫内膜异位症模型，并评价促性腺激素释放激素（gonadotropin-releasing hormone，GnRH）激动剂GenSci006对实验大鼠子宫内膜异位症模型的影响。 方法 取供体SPF级雌性SD大鼠的子宫内膜移植于受体雌性大鼠的腹腔壁上，构建同种异体的子宫内膜异位症模型。3周后，测量异位内膜的长、宽、高，计算给药前异位内膜的体积V1。将进行假手术操作的大鼠设为假手术组，将造模大鼠随机分为模型组、曲普瑞林组（0.25 mg/kg）、GenSci006-1组（0.125 mg/kg）和GenSci006-2组（0.25 mg/kg）共4组，每组大鼠16只。各组大鼠单次给予相应的药物，假手术组和模型组给予同等体积的溶剂。3周后，再次测量异位内膜，计算给药后异位内膜的体积V2和抑制率；通过比较脏器系数及病理切片的变化，判断GenSci006 对大鼠子宫和卵巢组织的影响；ELISA法测定血清中雌二醇（estradiol，E2）、孕酮（progesterone，P4）、卵泡刺激素（follicle stimulating hormone，FSH）和黄体生成素（luteinizing hormone，LH）水平的变化；实时荧光定量PCR法测定下丘脑和垂体中GnRH受体（GnRH receptor，GnRHR）mRNA的表达水平。蛋白质印迹法检测异位内膜组织中雌激素受体（estrogen receptor，ER）α、ERβ和孕激素受体（progesterone receptor，PR）蛋白的表达。 结果 给药3周后发现，与模型组相比，曲普瑞林组和GenSci006-2组大鼠的体重显著增加（P<0.05），而异位内膜的体积显著减小（P<0.05）。与假手术组相比，模型组子宫、卵巢脏器系数及子宫内膜厚度无明显变化（P>0.05）；与模型组相比，曲普瑞林组和GenSci006-2组子宫脏器系数及子宫内膜厚度显著降低（P<0.05）。与假手术组相比，模型组血清中E2、P4、FSH、LH水平无明显变化（P>0.05）；与模型组相比，曲普瑞林组、GenSci006-1组和GenSci006-2组大鼠的卵巢脏器系数和血清P4水平均显著降低（P<0.05），而GenSci006-1组大鼠的血清LH水平明显升高（P<0.05），但各组血清E2和FSH水平并无显著变化（P>0.05）。与模型组相比，曲普瑞林组和GenSci006-2组大鼠垂体GnRHR mRNA表达水平显著下调（P<0.05）；各组大鼠下丘脑组织中GnRHR mRNA表达及异位内膜组织中ERα、ERβ、PR蛋白表达水平无明显变化（P>0.05）。 结论 大鼠同种异体子宫内膜异位症模型适宜作为筛选和评价子宫内膜异位症治疗药物的动物模型，而且异位内膜体积、抑制率、子宫及卵巢脏器系数、血清E2水平均可作为检测药物疗效的指标。
中图分类号:
钟瑞华, 李国停, 杨文捷, 郭湘洁, 周洁芸, 胡颖怡, 倪其承, 杨野, 张敏, 朱焰. 同种异体子宫内膜异位症大鼠模型用于GnRH激动剂类药物的药效评价研究[J]. 实验动物与比较医学, 2024, 44(2): 127-138.
Ruihua ZHONG, Guoting LI, Wenjie YANG, Xiangjie GUO, Jieyun ZHOU, Yingyi HU, Qicheng NI, Ye YANG, Min ZHANG, Yan ZHU. Application of Allograft Endometriosis Rat Model in Pharmaco-dynamic Evaluation of GnRH Agonists[J]. Laboratory Animal and Comparative Medicine, 2024, 44(2): 127-138.
图1 GenSci006对同种异体移植子宫异位内膜症模型大鼠体重的影响注：Sham即假手术组，移植同种异体子宫周围的脂肪到大鼠腹壁，然后注射GenSci006专用溶剂；Model即模型组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射GenSci006专用溶剂；Triptorelin即曲普瑞林组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射曲普瑞林0.25 mg/kg；GenSci006-1和GenSci006-2组，移植同种异体子宫内膜组织到大鼠腹壁，然后分别注射0.125 mg/kg和 0.25 mg/kg的GenSci006。每组16只大鼠；与模型组相比，*P<0.05。
Figure 1 Effect of GenSci006 on body weight of allograft endometriosis rat modelNote：Sham group （n=16）， transplanted with fat tissues around the uterus and injected with GenSci006 specific solvent； Model group （n=16）， xenografted with endometrial tissues and injected with GenSci006 specific solvent； Triptorelin group（n=16）， xenografted with endometrial tissues and injected with 0.25 mg/kg triptorelin； GenSci006-1 and GenSci006-2 groups （each n=16）， xenografted with endometrial tissues and injected with 0.125 mg/kg and 0.25 mg/kg GenSci006， respectively. Compared with the model group， * P<0.05.
图2 GenSci006对同种异体移植子宫内膜异位症模型大鼠异位内膜的抑制作用注：A，给药前各组大鼠的异位内膜图片；B，给药后各组大鼠的异位内膜图片；C，给药3周后各组大鼠的异位内膜病理学特征（HE染色，×10）；D，给药前、后各组大鼠的异位内膜体积及抑制率。Sham即假手术组，移植同种异体子宫周围的脂肪到大鼠腹壁，然后注射GenSci006专用溶剂；Model即模型组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射GenSci006专用溶剂；Triptorelin即曲普瑞林组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射曲普瑞林0.25 mg/kg；GenSci006-1和GenSci006-2组，移植同种异体子宫内膜组织到大鼠腹壁，然后分别注射0.125 mg/kg和 0.25 mg/kg的GenSci006。每组16只大鼠；与模型组相比，*P<0.05。
Figure 2 Inhibitory effect of GenSci006 on ectopic endometrium in allograft endometriosis ratsNote： A， Pictures of ectopic endometrium before administration； B， Pictures of ectopic endometrium after administration；C， Pathological section of ectopic endometrium in endometriosis model rats（HE staining， ×10）；D， Tthe volume of ectopic endometrium before and after administration and the inhibition rate. Sham group （n=16）， transplanted with fat tissues around the uterus and injected with GenSci006 specific solvent； Model group （n=16）， xenografted with endometrial tissues and injected with GenSci006 specific solvent； Triptorelin group （n=16）， xenografted with endometrial tissues and injected with 0.25 mg/kg triptorelin； GenSci006-1 and GenSci006-2 groups （each n=16）， xenografted with endometrial tissues and injected with 0.125 mg/kg and 0.25 mg/kg GenSci006， respectively. Compared with the model group，*P<0.05.
图3 GenSci006对同种异体移植子宫内膜异位症模型大鼠子宫和卵巢的影响注：A示子宫组织病理切片（×10）；B示卵巢组织病理切片（×10），箭头所指处为生长卵泡；C示子宫、卵巢脏器系数和子宫组织的内膜厚度。Sham即假手术组，移植同种异体子宫周围的脂肪到大鼠腹壁，然后注射GenSci006专用溶剂；Model即模型组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射GenSci006专用溶剂；Triptorelin即曲普瑞林组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射曲普瑞林0.25 mg/kg；GenSci006-1和GenSci006-2组，移植同种异体子宫内膜组织到大鼠腹壁，然后分别注射0.125 mg/kg和 0.25 mg/kg的GenSci006。每组16只大鼠；与模型组相比，*P<0.05。
Figure 3 Effect of GenSci006 on uterus and ovary in allograft endometriosis ratsNote：A， Pathological section of uterus in endometriosis model rats （HE staining， ×10）；B， Ppathological section of ovary in endometriosis model rats （HE staining， ×10）； The arrow represents growth follicles；C， The coefficient of uterine organs，endometrial thickness and ovarian organ coefficient. Sham group （n=16）， transplanted with fat tissues around the uterus and injected with GenSci006 specific solvent； Model group （n=16）， xenografted with endometrial tissues and injected with GenSci006 specific solvent； Triptorelin group （n=16）， xenografted with endometrial tissues and injected with 0.25 mg/kg triptorelin； GenSci006-1 and GenSci006-2 groups （each n=16）， xenografted with endometrial tissues and injected with 0.125 mg/kg and 0.25 mg/kg GenSci006， respectively. Compared with the model group，*P<0.05
图 4 GenSci006对同种异体移植子宫内膜异位症模型大鼠血清E2、P4、FSH和LH水平的影响注：A，血清中雌二醇（E2 ）水平；B，血清中孕酮（P4）水平；C，血清中卵泡刺激素（FSH）水平；D，血清中黄体生成素（LH）水平。Sham即假手术组，移植同种异体子宫周围的脂肪到大鼠腹壁，然后注射GenSci006专用溶剂；Model即模型组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射GenSci006专用溶剂；Triptorelin即曲普瑞林组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射曲普瑞林0.25 mg/kg；GenSci006-1和GenSci006-2组，移植同种异体子宫内膜组织到大鼠腹壁，然后分别注射0.125 mg/kg和 0.25 mg/kg的GenSci006。每组8只大鼠；与模型组相比，*P<0.05；与曲普瑞林组相比，#P<0.05。
Figure 4 Effect of GenSci006 on serum levels of E2， P4， FSH and LH in allograft endometriosis ratsNote： A， Serum level of estradiol （E2）； B， Serum level of progesterone （P4）； C， Serum level of follicle stimulating hormone （FSH）； D， Serum level of luteinizing hormone （LH）. Sham group （n=8）， transplanted with fat tissues and injected with GenSci006 specific solvent； Model group （n=8）， xenografted with endometrial tissues around the uterus and injected with GenSci006 specific solvent； Triptorelin group （n=8）， xenografted with endometrial tissues and injected with 0.25 mg/kg triptorelin； GenSci006-1 and GenSci006-2 groups （each n=8）， xenografted with endometrial tissues and injected with 0.125 mg/kg and 0.25 mg/kg GenSci006， respectively. Compared with the model group， *P<0.05； Compared with the triptorelin group， #P<0.05.
图5 GenSci006对同种异体移植子宫内膜异位症模型大鼠下丘脑和垂体组织中GnRHR基因mRNA表达水平的影响注：A，下丘脑组织中促性腺激素释放激素受体（GnRHR） mRNA 表达；B，垂体组织中GnRHR mRNA 表达。Sham即假手术组，移植同种异体子宫周围的脂肪到大鼠腹壁，然后注射GenSci006专用溶剂；Model即模型组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射GenSci006专用溶剂；Triptorelin即曲普瑞林组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射曲普瑞林0.25 mg/kg；GenSci006-1和GenSci006-2组，移植同种异体子宫内膜组织到大鼠腹壁，然后分别注射0.125 mg/kg和 0.25 mg/kg的GenSci006。每组6只大鼠；与模型组相比，*P<0.05。
Figure 5 Effect of GenSci006 on GnRHR mRNA expression in hypothalamus and pituitary of allograft endometriosis ratsNote： A， Gonadotropin-releasing hormone receptor （GnRHR） mRNA expression in hypothalamus； B， GnRHR mRNA expression in pituitary. Sham group （n=6）， transplanted with fat tissues and injected with GenSci006 specific solvent； Model group （n=6）， xenografted with endometrial tissues around the uterus and injected with GenSci006 specific solvent； Triptorelin group （n=6）， xenografted with endometrial tissues and injected with 0.25 mg/kg triptorelin； GenSci006-1 and GenSci006-2 groups （each n=6）， xenografted with endometrial tissues and injected with 0.125 mg/kg and 0.25 mg/kg GenSci006， respectively. Compared with the model group， *P<0.05.
图6 GenSci006对同种异体移植子宫内膜异位症模型大鼠异位内膜组织中ERα、ERβ、PR蛋白表达的影响注：ERα/β，雌激素受体α/β；PR，孕激素受体。Model即模型组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射GenSci006专用溶剂；Triptorelin即曲普瑞林组，移植同种异体子宫内膜组织到大鼠腹壁，然后注射曲普瑞林0.25 mg/kg；GenSci006-1和GenSci006-2组，移植同种异体子宫内膜组织到大鼠腹壁，然后分别注射0.125 mg/kg和 0.25 mg/kg的GenSci006。每组6只大鼠。
Figure 6 Effect of GenSci006 on protein expression of ERα、ERβ、PR in ectopic endometrial tissues of allograft endometriosis rat modelNote： ERα/β， Estradiol receptor α/β； PR， Progesterone receptor. Model group （n=6）， xenografted with endometrial tissues around the uterus and injected with GenSci006 specific solvent； Triptorelin group （n=6）， xenografted with endometrial tissues and injected with 0.25 mg/kg triptorelin； GenSci006-1 and GenSci006-2 groups （each n=6）， xenografted with endometrial tissues and injected with 0.125 mg/kg and 0.25 mg/kg GenSci006， respectively.
| 1 | 中华医学会妇产科学分会子宫内膜异位症协作组. 子宫内膜异位症的诊治指南[J]. 中华妇产科杂志, 2015, 50(3):161-169. DOI: 10.3760/cma.j.issn.0529-567x.2015.03.001 . |
| Endometriosis Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association. Guidelines for diagnosis and treatment of endometriosis[J]. Chin J Obstet Gynecol, 2015, 50(3):161-169. DOI: 10.3760/cma.j.issn.0529-567x.2015.03.001 . | |
| 2 | TAYLOR H S, KOTLYAR A M, FLORES V A. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations[J]. Lancet, 2021, 397(10276):839-852. DOI: 10.1016/S0140-6736(21)00389-5 . |
| 3 | ALLAIRE C, BEDAIWY M A, YONG P J. Diagnosis and management of endometriosis[J]. CMAJ, 2023, 195(10): E363-E371. DOI: 10.1503/cmaj.220637 . |
| 4 | RAFIQUE S, DECHERNEY A H. Medical management of endometriosis[J]. Clin Obstet Gynecol, 2017, 60(3):485-496. DOI: 10.1097/GRF.0000000000000292 . |
| 5 | CAPEZZUOLI T, ROSSI M, LA TORRE F, et al. Hormonal drugs for the treatment of endometriosis[J]. Curr Opin Pharmacol, 2022, 67:102311. DOI: 10.1016/j.coph.2022.102311 . |
| 6 | KANELLOPOULOS D, KARAGIANNI D, PERGIALIOTIS V, et al. The effect of endometriosis on fertility in an animal model[J]. J Med Life, 2022, 15(9):1170-1175. DOI: 10.25122/jml-2021-0391 . |
| 7 | 钟瑞华, 周娴颖, 谢淑武, 等. 坤泰胶囊对大鼠实验性子宫异位内膜生长及其妊娠结局的影响[J]. 生殖与避孕, 2015, 1(8):517-524. |
| ZHONG R H, ZHOU X Y, XIE S W, et al. Effect of Kuntai capsule on ectopic endometrium and the pregnancy outcome in a rat of endometriosis[J]. Reprod Contracept, 2015, 1(8):517-524. | |
| 8 | LI H, YANG H D, LU S Y, et al. Autophagy-dependent ferroptosis is involved in the development of endometriosis[J]. Gynecol Endocrinol, 2023, 39(1):2242962. DOI: 10.1080/09513590.2023.2242962 . |
| 9 | KARSLıOGLU T, KARASU A F G, YILDIZ P. The effects of micronized progesterone and cabergoline on a rat autotransplantation endometriosis model: a placebo controlled randomized trial[J]. J Invest Surg, 2021, 34(8):897-901. DOI: 10.1080/08941939.2019.1705442 . |
| 10 | TEJADA M A, SANTOS-LLAMAS A I, ESCRIVA L, et al. Identification of altered evoked and non-evoked responses in a heterologous mouse model of endometriosis-associated pain[J]. Biomedicines, 2022, 10(2):501. DOI: 10.3390/biomedicines10020501 . |
| 11 | VERNON M W, WILSON E A. Studies on the surgical induction of endometriosis in the rat[J]. Fertil Steril, 1985, 44(5):684-694. |
| 12 | ZHONG R H, MA A Y, ZHU J P, et al. Kuntai capsule inhibited endometriosis via inducing apoptosis in a rat model[J]. Evid Based Complement Alternat Med, 2016, 2016:5649169. DOI: 10.1155/2016/5649169 . |
| 13 | ZHANG J F, ZHU Y, ZHOU X Y, et al. Evaluation of biodegradable microspheres containing nomegestrol acetate in a rat model of endometriosis[J]. Eur J Pharm Sci, 2014, 65:15-20. DOI: 10.1016/j.ejps.2014.08.011 . |
| 14 | 张薇, 邹移海, 胡海勋, 等. 同种异体移植子宫内膜异位症大鼠模型的建立[J]. 热带医学杂志, 2010, 10(7):770-772. |
| ZHANG W, ZOU Y H, HU H X, et al. Establishment of an allograft rat model for the study of endmetriosis[J]. J Trop Med, 2010, 10(7):770-772. | |
| 15 | 孙伟伟, 常欢, 赵瑞华. 活血消异方对子宫内膜异位症大鼠生育力和早期妊娠毒性的影响[J]. 药物评价研究, 2019, 42(4):648-652. DOI: 10.7501/j.issn.1674-6376.2019.04.008 . |
| SUN W W, CHANG H, ZHAO R H. Effect of Huoxue Xiaoyi Prescription on fertility and early pregnancy toxicity of rats with endometriosis[J]. Drug Eval Res, 2019, 42(4):648-652. DOI: 10.7501/j.issn.1674-6376.2019.04.008 . | |
| 16 | 崔金秀, 顾振鹏, 刘志慧, 等. 同种异体Sprague-Dawley大鼠子宫内膜异位症动物模型的建立[J]. 中华妇幼临床医学杂志(电子版), 2015, 11(3):388-392. DOI: 10.3877/cma.j.issn.1673-5250.2015.03.022 . |
| CUI J X, GU Z P, LIU Z H, et al. Establishment of endometriosis model in allogeneic Sprague-Dawley rats[J]. Chin J Obstet Gynecol Pediatr Electron Ed, 2015, 11(3):388-392. DOI: 10.3877/cma.j.issn.1673-5250.2015.03.022 . | |
| 17 | 崔阳阳, 孙伟伟, 赵瑞华. 子宫内膜异位症动物模型研究进展[J]. 中国实验动物学报, 2013, 21(5):86-89, 94. DOI: 10.3969/j.issn.1005-4847.2013.05.018 . |
| CUI Y Y, SUN W W, ZHAO R H. Recent advances in research on animal models of endometriosis[J]. Acta Lab Animalis Sci Sin, 2013, 21(5):86-89, 94. DOI: 10.3969/j.issn.1005-4847.2013.05.018 . | |
| 18 | TOMAYKO M M, REYNOLDS C P. Determination of subcutaneous tumor size in athymic (nude) mice[J]. Cancer Chemother Pharmacol, 1989, 24(3):148-154. DOI: 10.1007/BF00300234 . |
| 19 | UYGUR D, AYTAN H, ZERGEROGLU S, et al. Leflunomide: an immunomodulator: induces regression of endometrial explants in a rat model of endometriosis[J]. J Soc Gynecol Investig, 2006, 13(5):378-383. DOI: 10.1016/j.jsgi.2006.03.006 . |
| 20 | 唐艳, 张莉, 刘海红. 川芎嗪抑制TLR4/MyD88/NF-κB信号通路减轻子宫内膜异位症大鼠炎症反应[J]. 免疫学杂志, 2023, 39(6):469-477. DOI: 10.13431/j.cnki.immunol.j.20230061 . |
| TANG Y, ZHANG L, LIU H H. Ligustrazine mitigates inflammatory response in endometriosis rats by inhibiting TLR4/MyD88/NF-κB signaling pathway[J]. Immunol J, 2023, 39(6):469-477. DOI: 10.13431/j.cnki.immunol.j.20230061 . | |
| 21 | 单婧, 程雯, 翟东霞, 等. 子宫内膜异位症啮齿类动物模型研究进展[J]. 生殖医学杂志, 2017, 26(5):498-501. DOI: 10.3969/j.issn.1004-3845.2017.05.022 . |
| SHAN J, CHENG W, ZHAI D X, et al. Research progress of rodent model with endometriosis[J]. J Reprod Med, 2017, 26(5):498-501. DOI: 10.3969/j.issn.1004-3845.2017.05.022 . | |
| 22 | BERGQVIST A, BERGH T, HOGSTRÖM L, et al. Effects of triptorelin versus placebo on the symptoms of endometriosis[J]. Fertil Steril, 1998, 69(4):702-708. DOI: 10.1016/s0015-0282(98)00019-3 . |
| 23 | TESONE M, BILOTAS M, BARAÑAO R I, et al. The role of GnRH analogues in endometriosis-associated apoptosis and angiogenesis[J]. Gynecol Obstet Invest, 2008, 66():10-18. DOI: 10.1159/000148026 . |
| 24 | KHAN K N, KITAJIMA M, HIRAKI K, et al. Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy[J]. Hum Reprod, 2010, 25(3):642-653. DOI: 10.1093/humrep/dep437 . |
| 25 | EMONS G, SCHALLY A V. The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers[J]. Hum Reprod, 1994, 9(7):1364-1379. DOI: 10.1093/oxfordjournals.humrep.a138714 . |
| 26 | GRÜNDKER C, GÜNTHERT A R, WESTPHALEN S, et al. Biology of the gonadotropin-releasing hormone system in gynecological cancers[J]. Eur J Endocrinol, 2002, 146(1):1-14. DOI: 10.1530/eje.0.1460001 . |
| 27 | SUKUMAR J S, QUIROGA D, KASSEM M, et al. Patient preferences and adherence to adjuvant GnRH analogs among premenopausal women with hormone receptor positive breast cancer[J]. Breast Cancer Res Treat, 2021, 190(2):183-188. DOI: 10.1007/s10549-021-06368-4 . |
| 28 | 郎景和, 冷金花, 王泽华, 等. 促性腺激素释放激素激动剂在子宫内膜异位症和子宫平滑肌瘤治疗中的应用专家意见[J]. 中华妇产科杂志, 2017, 52(2):77-81. DOI: 10.3760/cma.j.issn.0529-567x.2017.02.002 . |
| LANG J H, LENG J H, WANG Z H, et al. Expert opinion on the application of gonadotropin-releasing hormone agonist in the treatment of endometriosis and uterine leiomyoma[J]. Chin J Obstet Gynecol, 2017, 52(2):77-81. DOI: 10.3760/cma.j.issn.0529-567x.2017.02.002 . | |
| 29 | BROWN J, PAN A, HART R J. Gonadotrophin-releasing hormone analogues for pain associated with endometriosis[J]. Cochrane Database Syst Rev, 2010, 2010(12): CD008475. DOI: 10.1002/14651858.CD008475.pub2 . |
| [1] | 胡锦华, 韩菁婕, 金旻, 胡滨, 娄月芬. 葛根素对大鼠和小鼠骨密度影响的Meta分析[J]. 实验动物与比较医学, 2024, 44(2): 149-161. |
| [2] | 侯敏博, 崔甜甜, 苏娜瑛, 张苗苗, 焦永敏, 严建燕, 汪溪洁, 大平东子. 一例Han-Wistar大鼠垂体细胞瘤的病理学分析[J]. 实验动物与比较医学, 2023, 43(6): 654-658. |
| [3] | 赵丽亚, 倪丽菊, 张彩勤, 汤建平, 姚养正, 聂艳艳, 顾晓雪, 赵莹. 基于多重PCR-LDR技术建立近交系大鼠单核苷酸多态性遗传检测方案[J]. 实验动物与比较医学, 2023, 43(5): 548-558. |
| [4] | 于灵芝, 谢建芸, 冯丽萍, 魏晓锋. 金黄色葡萄球菌荧光定量PCR检测方法的建立及其在大鼠、小鼠粪便检测中的应用[J]. 实验动物与比较医学, 2023, 43(5): 566-573. |
| [5] | 黄缨, 韦思羽, 蔡莉, 强苏静, 李冬婷, 丁玉强. 供应商来源的实验大鼠和小鼠微生物监测结果分析：以复旦大学实验动物科学部为例[J]. 实验动物与比较医学, 2023, 43(4): 347-354. |
| [6] | 黄慧, 邓亚胜, 梁天薇, 郑艺清, 范燕萍, 荣娜, 林江. 卵巢储备功能减退动物模型的造模方法评价与分析[J]. 实验动物与比较医学, 2023, 43(4): 422-428. |
| [7] | 夏子茵, 柴媛媛, 徐云霞, 俞沁玮, 黄鑫, 张陆勇, 江振洲. 大鼠血清尿酸液相色谱-紫外检测新方法的建立及比较研究[J]. 实验动物与比较医学, 2023, 43(3): 314-322. |
| [8] | 谭莹, 廖文平, 高启龙, 李勇, 史新辉, 王京昆. 碘酸钠诱发视网膜色素变性大鼠模型的生理指标和组织病理学分析[J]. 实验动物与比较医学, 2023, 43(2): 124-135. |
| [9] | 葛健, 孙静芬, 吴永杰. 牛磺酸对苯扎氯铵损伤大鼠眼角膜内皮细胞无保护作用[J]. 实验动物与比较医学, 2023, 43(1): 39-43. |
| [10] | 许琴, 倪艳, 是文辉, 李建瑛, 刘江伟, 赵红琼, 徐新明. SPF级雄性SD大鼠回肠与结肠菌群结构比较分析[J]. 实验动物与比较医学, 2023, 43(1): 53-60. |
| [11] | 杨丽雅, 宋涛, 何佳璘, 郭一鸣, 亓明康, 王含必, 王慧萍. 阴道萎缩大鼠模型的建立及在药效评价中的应用[J]. 实验动物与比较医学, 2022, 42(6): 531-540. |
| [12] | 吴斌, 王旭, 付东旭, 朱宇均, 黄金路, 朱顺星. 疏肝解郁方对便秘型肠易激综合征大鼠模型的疗效及脑-肠轴功能的影响[J]. 实验动物与比较医学, 2022, 42(6): 551-559. |
| [13] | 黄少凤, 林忠, 朱雪红, 刘姝岑, 宾力. 宫腔粘连大鼠模型研究进展[J]. 实验动物与比较医学, 2022, 42(6): 560-565. |
| [14] | 高晨, 凡春玲, 李玉荣, 裴文娟, 关彩萍. 模拟高原低氧环境下运动疲劳大鼠脑皮层单羧酸转运蛋白的变化及其意义[J]. 实验动物与比较医学, 2022, 42(5): 384-392. |
| [15] | 许冰馨, 范凯健, 王婷玉, 陈慧瑾. 地塞米松对胶原诱导性关节炎大鼠模型软骨退化的改善作用[J]. 实验动物与比较医学, 2022, 42(5): 416-422. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||
