不同浓度环磷酰胺诱导早发性卵巢功能不全小鼠模型及作用机制研究

doi:10.12300/j.issn.1674-5817.2024.194

实验动物与比较医学 ›› 2025, Vol. 45 ›› Issue (4): 403-410.DOI: 10.12300/j.issn.1674-5817.2024.194

不同浓度环磷酰胺诱导早发性卵巢功能不全小鼠模型及作用机制研究

贡磊磊¹(), 王晓霞², 封学伟¹, 李心蕾¹, 赵涵¹, 张雪艳¹()(), 冯欣¹()

^1.首都医科大学附属北京妇产医院/北京妇幼保健院, 北京 100026
^2.北京市肛肠医院, 北京 100120

收稿日期:2025-01-02 修回日期:2025-04-22 出版日期:2025-08-25 发布日期:2025-09-01
通讯作者: 张雪艳（1969—），女，学士，副主任药师，研究方向：妇产科临床药学。E-mail：xueyan625@ccmu.edu.cn。ORCID： 0009-0007-6631-9363；
冯欣（1965—），女，硕士，主任药师，研究方向：妇产科临床药学。E-mail：fengxin1115@ccmu.edu.cn。ORCID: 0000-0002-6296-0321
作者简介:贡磊磊（1989—），男，博士，主管药师，研究方向：妇产科中药药理学及临床药学。E-mail：gl890925@ccmu.edu.cn
基金资助:
国家自然科学基金青年科学基金项目“SIRT5驱动FOXO3a去乙酰化保护卵母细胞免受氧化损伤改善早发性卵巢功能不全及坤泰成方干预作用”(82204698)

A Mouse Model and Mechanism Study of Premature Ovarian Insufficiency Induced by Different Concentrations of Cyclophosphamide

GONG Leilei¹(), WANG Xiaoxia², FENG Xuewei¹, LI Xinlei¹, ZHAO Han¹, ZHANG Xueyan¹()(), FENG Xin¹()

^1.Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China
^2.Beijing Rectum Hospital, Beijing 100120, China

Received:2025-01-02 Revised:2025-04-22 Published:2025-08-25 Online:2025-09-01
Contact: ZHANG Xueyan (ORCID: 0009-0007-6631-9363 ), E-mail: xueyan625@ccmu.edu.cn;
FENG Xin (ORCID: 0000-0002-6296-0321), E-mail: fenxin1115@ccmu.edu.cn;

摘要/Abstract

摘要：

目的观察比较不同浓度环磷酰胺（cyclophosphamide， CTX）诱导小鼠早发性卵巢功能不全（premature ovarian insufficiency，POI）模型的效果并探讨损伤机制。方法 32只6~8周龄的C57BL/6J雌性小鼠按体重随机区组法分为4组，每组8只，分别用75 mg/kg CTX、120 mg/kg CTX、120 mg/kg CTX+12 mg/kg 白消安（Busulfan）和同体积生理盐水腹腔单次注射来建立POI模型，测定每组小鼠的卵巢系数、血清中雌二醇（estradiol，E₂）和卵泡刺激素（follicle stimulating hormone，FSH）水平，并通过蛋白质印迹法检测不同造模浓度条件下卵巢组织内NAD依赖性蛋白脱酰酶5（NAD-dependent deacetylase sirtuin-5，SIRT5）和叉头框蛋白O3a（forkhead box protein O3a，FOXO3a）蛋白表达水平的变化规律。筛选最佳造模浓度后，将40只6~8周龄的C57BL/6J雌性小鼠按体重随机区组法分为5组，每组8只；以生理盐水作为对照，用120 mg/kg CTX造模后第1、2、7、14天，通过蛋白质印迹法检测不同造模时间内卵巢组织中SIRT5和FOXO3a蛋白表达水平的变化规律。结果与生理盐水对照组比较，不同浓度的CTX（75 mg/kg和120 mg/kg）和120 mg/kg CTX+12 mg/kg Busulfan均可以诱导小鼠出现POI损伤，其中120 mg/kg CTX造模小鼠的卵巢系数（P<0.001）和E₂水平变化较小（P<0.05），120 mg/kg CTX+12 mg/kg Busulfan组小鼠被毛粗糙，光泽度下降，反应迟钝，状态最差。与生理盐水对照组相比，75 mg/kg CTX造模组小鼠的卵巢组织中FOXO3a表达显著下调（P<0.05），SIRT5表达没有显著变化（P＞0.05），而120 mg/kg CTX造模组的SIRT5（P<0.05）和FOXO3a（P<0.05）表达均显著下调。120 mg/kg CTX造模后第2和7天，SIRT5（P<0.01）和FOXO3a（P<0.001）表达均显著下调，且第7天时表达水平变化最大（SIRT5，P<0.000 1；FOXO3a，P<0.000 1）。结论 120 mg/kg CTX诱导小鼠POI模型的卵巢损伤小于75 mg/kg CTX诱导的POI模型，并且120 mg/kg CTX造模第7天的SIRT5和FOXO3a表达变化最为显著，其作用机制可能与SIRT5-FOXO3a通路活性受抑制相关。

关键词: 环磷酰胺, 早发性卵巢功能不全, 小鼠模型, SIRT5-FOXO3a通路

Abstract:

Objective To observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. Methods Thirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. Results Compared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). Conclusion Ovarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

Key words: Cyclophosphamide, Premature ovarian insufficiency, Mouse model, SIRT5-FOXO3a pathway

中图分类号:

Q95-33

贡磊磊,王晓霞,封学伟,等. 不同浓度环磷酰胺诱导早发性卵巢功能不全小鼠模型及作用机制研究[J]. 实验动物与比较医学, 2025, 45(4): 403-410. DOI: 10.12300/j.issn.1674-5817.2024.194.

GONG Leilei,WANG Xiaoxia,FENG Xuewei,et al. A Mouse Model and Mechanism Study of Premature Ovarian Insufficiency Induced by Different Concentrations of Cyclophosphamide[J]. Laboratory Animal and Comparative Medicine, 2025, 45(4): 403-410. DOI: 10.12300/j.issn.1674-5817.2024.194.

图/表 3

图1 CTX或CTX+Busulfan造模后第7天的小鼠卵巢系数和血清激素变化水平注：A，第一批次小鼠卵巢系数；B，第一批次小鼠血清E2测定值；C，第一批次小鼠血清FSH测定值。Ctl为对照组；75 CTX、120 CTX、120 CTX+12 Busulfan分别代表通过腹腔注射75 mg/kg环磷酰胺（CTX）、120 mg/kg CTX、120 mg/kg CTX+12 mg/kg白消安（Busulfan）构建的早发性卵巢功能不全模型组；E2为雌二醇；FSH为卵泡刺激素。与对照组比较（n=8），?P<0.05，??P<0.01，???P<0.001。

Figure 1 Ovarian coefficients and changes of serum hormone levels in mice on day 7 after modeling with CTX or CTX+BusulfanNote： A， Ovarian index of the first batch of mice； B， Serum E2 levels in the first batch of mice； C， Serum FSH levels in the first batch of mice. Ctl represents control group； 75 CTX， 120 CTX， 120 CTX+12 Busulfan represents premature ovarian insufficiency model group established by intraperitoneal injection of 75 mg/kg cyclophosphamide （CTX）， 120 mg/kg CTX， 120 mg/kg CTX+12 mg/kg Busulfan respectively； E2 represents estradiol； FSH represents follicle-stimulating hormone. Compared with Ctl （n=8）， ?P<0.05， ??P<0.01， ???P<0.001.

图2 不同浓度的CTX和CTX+Busulfan造模后第7天卵巢组织SIRT5和FOXO3a表达情况注：A，不同浓度CTX及CTX+Busulfan造模后第7天SIRT5和FOXO蛋白质印迹图；B，不同浓度CTX及CTX+Busulfan造模后第7天SIRT5蛋白表达变化；C，不同浓度CTX及CTX+Busulfan造模后第7天FOXO3a蛋白表达变化。与对照组比较（n=8），?P<0.05，??P<0.01。

Figure 2 Expressions of SIRT5 and FOXO3a in ovarian tissues on day 7 after modeling with different concentrations of CTX and CTX+BusulfanNote： A， Western blot results of SIRT5 and FOXO3a proteins on day 7 after modeling with different concentrations of CTX and CTX+Busulfan； B， The expression of SIRT5 on day 7 after modeling with different concentrations of CTX and CTX + Busulfan； C， The expression of FOXO3a on day 7 after modeling with different concentrations of CTX and CTX + Busulfan. Compared with Ctl （n=8）， ?P<0.05， ??P<0.01.

图3 120 mg/kg CTX造模不同时间后小鼠卵巢组织SIRT5和FOXO3a表达变化情况注：A和E，造模后第1天 FOXO3a和SIRT5表达变化；B和F，造模后第2天 FOXO3a和SIRT5表达变化；C和G，造模后第7天 FOXO3a和SIRT5表达变化；D和H，造模后第14天 FOXO3a和SIRT5表达变化；I，造模后第1天 FOXO3a和SIRT5蛋白质印迹图；J，造模后第2天 FOXO3a和SIRT5蛋白质印迹图；K，造模后第7天 FOXO3a和SIRT5蛋白质印迹图；L，造模后第14天 FOXO3a和SIRT5蛋白质印迹图。与对照组比较（n=5），??P<0.01，???P<0.001，????P<0.000 1。

Figure 3 Expression of SIRT5 and FOXO3a in mouse ovarian tissue at different times after 120 mg/kg CTX modelingNote： A and E， The expression of FOXO3a and SIRT5 on day 1 after modeling； B and F， The expression of FOXO3a and SIRT5 on day 2 after modeling； C and G， The expression of FOXO3a and SIRT5 on day 7 after modeling； D and H， The expression of FOXO3a and SIRT5 on day 14 after modeling； I， Western blot results of FOXO3a and SIRT5 on day 1 after modeling； J， Western blot results of FOXO3a and SIRT5 on day 2 after modeling； K， Western blot results of FOXO3a and SIRT5 on day 7 after modeling； L， Western blot results of FOXO3a and SIRT5 on day 14 after modeling. Compared with Ctl （n=5）， ??P<0.01， ???P<0.001， ????P<0.000 1.

参考文献 30

[1]	中华医学会妇产科学分会绝经学组. 早发性卵巢功能不全的临床诊疗专家共识(2023版)[J]. 中华妇产科杂志, 2023, 58(10):721-728. DOI: 10.3760/cma.j.cn112141-20230316-00122 .
	Menopausal Group of Obstetrics and Gynecology Branch of Chinese Medical Association. Expert consensus on clinical diagnosis and treatment of early-onset ovarian insufficiency (2023 edition)[J]. Chin J Obstet Gynecol, 2023, 58(10):721-728. DOI: 10.3760/cma.j.cn112141-20230316-00122 .
[2]	PANAY N, ANDERSON R A, BENNIE A, et al. Evidence-based guideline: premature ovarian insufficiency[J]. Hum Reprod Open, 2024, 2024(4): hoae065. DOI:10.1093/hropen/hoae065 .
[3]	冯晓玲, 李力, 曲凡, 等. 早发性卵巢功能不全中西医结合诊疗指南[J]. 中医杂志, 2022, 63(12):1193-1198. DOI: 10.13288/j.11-2166/r.2022.12.017 .
	FENG X L, LI L, QU F, et al. Guideline for the diagnosis and treatment of premature ovarian insufficiency with integrated traditional Chinese and western medicine[J]. J Tradit Chin Med, 2022, 63(12):1193-1198. DOI: 10.13288/j.11-2166/r.2022.12.017 .
[4]	LI M, ZHU Y, WEI J, et al. The global prevalence of premature ovarian insufficiency: a systematic review and meta-analysis[J]. Climacteric, 2023, 26(2):95-102. DOI:10.1080/13697137.2022.2153033 .
[5]	吴洁, 郁琦. 早发性卵巢功能不全的诊断和处理[J]. 中华医学信息导报, 2016(21):21. DOI: 10.3969/j.issn.2095-6606.2024.01.015 .
	WU J, YU Q. Diagnosis and treatment of early-onset ovarian insufficiency[J]. China Med News, 2016(21):21. DOI: 10.3969/j.issn.2095-6606.2024.01.015 .
[6]	RUTH K S, DAY F R, HUSSAIN J, et al. Genetic insights into biological mechanisms governing human ovarian ageing[J]. Nature, 2021, 596(7872):393-397. DOI:10.1038/s41586-021-03779-7 .
[7]	王艳辉, 唐丽, 雷磊. 基于数据挖掘的早发性卵巢功能不全动物模型分析[J]. 中国实验方剂学杂志, 2023, 29(9):225-233. DOI: 10.13422/j.cnki.syfjx.20230317 .
	WANG Y H, TANG L, LEI L. Animal model of premature ovarian insufficiency based on data mining[J]. Chin J Exp Tradit Med Formulae, 2023, 29(9):225-233. DOI: 10.13422/j.cnki.syfjx.20230317 .
[8]	HUANG C Z, ZHAO S M, YANG Y J, et al. TP63 gain-of-function mutations cause premature ovarian insufficiency by inducing oocyte apoptosis[J]. J Clin Invest, 2023, 133(5): e162315. DOI:10.1172/JCI162315 .
[9]	FANOURIAKIS A, KOSTOPOULOU M, CHEEMA K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis[J]. Ann Rheum Dis, 2020, 79(6):713-723. DOI:10.1136/annrheumdis-2020-216924 .
[10]	QIN X S, ZHAO Y, ZHANG T Y, et al. TrkB agonist antibody ameliorates fertility deficits in aged and cyclophosphamide-induced premature ovarian failure model mice[J]. Nat Commun, 2022, 13(1):914. DOI:10.1038/s41467-022-28611-2 .
[11]	DING C Y, ZHU L P, SHEN H, et al. Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7[J]. Stem Cells, 2020, 38(9):1137-1148. DOI:10.1002/stem.3204 .
[12]	LIU M Y, ZHANG D, ZHOU X W, et al. Cell-free fat extract improves ovarian function and fertility in mice with premature ovarian insufficiency[J]. Stem Cell Res Ther, 2022, 13(1):320. DOI:10.1186/s13287-022-03012-w .
[13]	MO J H, HU H, LI P D, et al. Human hair follicle-derived mesenchymal stem cells improve ovarian function in cyclophosphamide-induced POF mice[J]. Stem Cell Res Ther, 2025, 16(1):67. DOI:10.1186/s13287-024-04097-1 .
[14]	BHARDWAJ J K, BIKAL P, SACHDEVA S N. Chemotherapeutic drugs induced female reproductive toxicity and treatment strategies[J]. J Biochem Mol Toxicol, 2023, 37(7): e23371. DOI:10.1002/jbt.23371 .
[15]	SWIGONSKA S, NYNCA A, MOLCAN T, et al. The role of lncRNAs in the protective action of tamoxifen on the ovaries of tumor-bearing rats receiving cyclophosphamide[J]. Int J Mol Sci, 2024, 25(23):12538. DOI:10.3390/ijms252312538 .
[16]	YAO Y, WANG B, YU K H, et al. Nur77 ameliorates cyclophosphamide-induced ovarian insufficiency in mice by inhibiting oxidative damage and cell senescence[J]. J Ovarian Res, 2024, 17(1):203. DOI:10.1186/s13048-024-01532-y .
[17]	LANDE Y, FISCH B, TSUR A, et al. Short-term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro [J]. Reprod Biomed Online, 2017, 34(1):104-114. DOI:10.1016/j.rbmo.2016. 10.005 .
[18]	YUKSEL A, BILDIK G, SENBABAOGLU F, et al. The magnitude of gonadotoxicity of chemotherapy drugs on ovarian follicles and granulosa cells varies depending upon the category of the drugs and the type of granulosa cells[J]. Hum Reprod, 2015, 30(12):2926-2935. DOI:10.1093/humrep/dev256 .
[19]	DI EMIDIO G, D'AURORA M, PLACIDI M, et al. Pre-conceptional maternal exposure to cyclophosphamide results in modifications of DNA methylation in F1 and F2 mouse oocytes: evidence for transgenerational effects[J]. Epigenetics, 2019, 14(11):1057-1064. DOI:10.1080/15592294. 2019.1631111 .
[20]	PETRILLO S K, DESMEULES P, TRUONG T Q, et al. Detection of DNA damage in oocytes of small ovarian follicles following phosphoramide mustard exposures of cultured rodent ovaries in vitro [J]. Toxicol Appl Pharmacol, 2011, 253(2):94-102. DOI:10.1016/j.taap.2011.03.012 .
[21]	AI G H, MENG M, GUO J, et al. Adipose-derived stem cells promote the repair of chemotherapy-induced premature ovarian failure by inhibiting granulosa cells apoptosis and senescence[J]. Stem Cell Res Ther, 2023, 14(1):75. DOI:10.1186/s13287-023-03297-5 .
[22]	LUAN Y, EDMONDS M E, WOODRUFF T K, et al. Inhibitors of apoptosis protect the ovarian reserve from cyclophosphamide[J]. J Endocrinol, 2019, 240(2):243-256. DOI:10.1530/JOE-18-0370 .
[23]	NGUYEN Q N, ZERAFA N, LIEW S H, et al. Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility[J]. Cell Death Dis, 2018, 9(6):618. DOI:10.1038/s41419-018-0633-7 .
[24]	JEELANI R, KHAN S N, SHAEIB F, et al. Cyclophosphamide and acrolein induced oxidative stress leading to deterioration of metaphase Ⅱ mouse oocyte quality[J]. Free Radic Biol Med, 2017, 110:11-18. DOI:10.1016/j.freeradbiomed. 2017.05.006 .
[25]	CHEN Y, ZHAO Y, MIAO C Y, et al. Quercetin alleviates cyclophosphamide-induced premature ovarian insufficiency in mice by reducing mitochondrial oxidative stress and pyroptosis in granulosa cells[J]. J Ovarian Res, 2022, 15(1):138. DOI:10.1186/s13048-022-01080-3 .
[26]	GONG L L, HOU J L, YANG H J, et al. Kuntai capsule attenuates premature ovarian insufficiency by activating the FOXO3/SIRT5 signaling pathway in mice: A comprehensive study using UHPLC-LTQ-Orbitrap and integrated pharmacology[J]. J Ethnopharmacol, 2024, 322:117625. DOI:10.1016/j.jep.2023. 117625 .
[27]	PACELLA-INCE L, ZANDER-FOX D L, LANE M. Mitochondrial SIRT5 is present in follicular cells and is altered by reduced ovarian reserve and advanced maternal age[J]. Reprod Fertil Dev, 2014, 26(8):1072-1083. DOI:10.1071/RD13178 .
[28]	CASTRILLON D H, MIAO L L, KOLLIPARA R, et al. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a[J]. Science, 2003, 301(5630):215-218. DOI:10.1126/science.1086336 .
[29]	KUMAR S, LOMBARD D B. Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology[J]. Crit Rev Biochem Mol Biol, 2018, 53(3):311-334. DOI:10.1080/10409238. 2018.1458071 .
[30]	WANG Y F, ZHU Y B, XING S G, et al. SIRT5 prevents cigarette smoke extract-induced apoptosis in lung epithelial cells via deacetylation of FOXO3[J]. Cell Stress Chaperones, 2015, 20(5):805-810. DOI:10.1007/s12192-015-0599-7 .

不同浓度环磷酰胺诱导早发性卵巢功能不全小鼠模型及作用机制研究

A Mouse Model and Mechanism Study of Premature Ovarian Insufficiency Induced by Different Concentrations of Cyclophosphamide

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 30

相关文章 15

编辑推荐

Metrics

本文评价

[1]	姜娟, 宋宁, 连文博, 邵丛丛, 顾文文, 石燕. 两种浓度乙醇溶液灌注建立小鼠宫腔粘连模型的组织病理和分子病理表型比较[J]. 实验动物与比较医学, 2025, 45(4): 393-402.
[2]	罗莲莲, 袁艳春, 王俊岭, 时广森. 肌萎缩侧索硬化症小鼠模型研究进展[J]. 实验动物与比较医学, 2025, 45(3): 290-299.
[3]	马婧威, 李根, 杨杨, 臧彩霞, 鲍秀琦, 张丹. 环磷酰胺诱导生精障碍小鼠模型不同恢复期的比较研究[J]. 实验动物与比较医学, 2023, 43(2): 112-123.
[4]	于士颜. 小鼠模型在消化道黏膜免疫及感染性疾病研究中的应用进展[J]. 实验动物与比较医学, 2022, 42(1): 3-10.
[5]	姚玎, 周晶, 严国锋, 王会阳, 汪雅荻, 马政文. 盐敏感性高血压小鼠模型的建立[J]. 实验动物与比较医学, 2020, 40(4): 314-.
[6]	柴文君, 孙磊, 刘晓丽, 潘洪玉, 郭天安, 徐烨, 闫明霞. 超声引导下左心室内注射人肺癌细胞建立骨转移小鼠模型[J]. 实验动物与比较医学, 2020, 40(3): 183-.
[7]	蒋红利, 马红叶, 薛瑾虹, 孙凌霜, 陈蕾. 绒毛蛋白1在单侧肾切除Habu肾炎小鼠模型中的作用[J]. 实验动物与比较医学, 2020, 40(1): 1-8.
[8]	李慧. Foxp2小鼠模型中发育性言语障碍的分子遗传学研究[J]. 实验动物与比较医学, 2019, 39(4): 331-336.
[9]	何一旻, 顾鸣敏. Myh13敲除小鼠表型的初步分析[J]. 实验动物与比较医学, 2019, 39(3): 193-200.
[10]	沈艳, 王韵, 张汝, 阮铮, 毛建华. 两种小鼠肺癌模型的构建及Micro PET-CT观察[J]. 实验动物与比较医学, 2019, 39(1): 39-45.
[11]	沈艳, 徐汪洋, 朱后保. 氧化还原酶DHTKD1基因突变致病机制及小鼠模型研究进展[J]. 实验动物与比较医学, 2018, 38(6): 468-472.
[12]	纪莲, 马铁, 狄正鸿, 刘冬妍. 小鼠特应性皮炎建模方法的改进[J]. 实验动物与比较医学, 2018, 38(4): 267-271.
[13]	顾晓雯, 孙瑞林, 费俭. Afp-cre-lacZ转基因小鼠的构建[J]. 实验动物与比较医学, 2017, 37(2): 89-93.
[14]	宋莹, 郭雅娟, 黄铭倩, 梁金强, 黄芝瑛. 不同因素对环磷酰胺诱导的免疫抑制小鼠模型效果的影响[J]. 实验动物与比较医学, 2017, 37(1): 36-39.
[15]	顾云浩, 曹晨洁, 胡碧原, 王俊, 韩东冬, 许爱华. PFC体内递增诱导建立S180肿瘤多药耐药模型及其稳定性观察[J]. 实验动物与比较医学, 2015, 35(5): 367-373.