CMTM2改善环磷酰胺致转基因小鼠模型生殖毒性作用并影响StAR蛋白的表达  

CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity and regulates StAR expression in a transgenic mouse model

作　　者：刘振华[1] 谢京[1] 萧云备[1] 张晓威[1] 袁也晴[1] 赵永平[1] 张国喜[1] 徐涛[1] 王晓峰[1] 

机构地区：[1]北京大学人民医院泌尿外科,北京100044

出　　处：《中华男科学杂志》2013年第3期210-213,共4页National Journal of Andrology

基　　金：北京市自然科学基金(7102152)~~

摘　　要：目的:探讨在转基因小鼠模型中CMTM2能否改善环磷酰胺(CP)引起的生殖毒性作用以及其对固醇合成快速调节蛋白(StAR)表达的影响。方法:随机选取CMTM2转基因小鼠20只分成2组:CMTM2+CP[CMTM2转基因小鼠腹腔内连续7 d注射50 mg/(kg.d)CP]组和CMTM2+NS(CMTM2转基因小鼠腹腔内连续7 d注射等量生理盐水)组,另取同源野生型C57BL/6J小鼠20只分成2组:WT+CP[野生型C57BL/6J小鼠腹腔内连续7 d注射50 mg/(kg.d)CP]组和WT+NS(野生型C57BL/6J小鼠腹腔内连续7 d注射等量生理盐水)组。30 d后各组小鼠处死取相应标本,放免法检测血清睾酮水平,分析各组小鼠精子浓度、精子活动率差异,Western印迹检测睾丸StAR蛋白表达。结果:对比CMTM2+NS组,CP能够降低CMTM2+CP组小鼠的血清睾酮含量[(42.98±3.25)nmol/L vs(46.74±3.38)nmol/L]、精子浓度[(16.89±1.17)×106/ml vs(24.68±0.95)×106/ml]以及精子活动率[(72.75±1.25)%vs(85.14±1.12)%](P<0.05),表现出明显的生殖毒性;对比WT+CP组,CMTM2+CP组小鼠血清睾酮[(42.98±3.25)nmol/L vs(37.97±4.17)nmol/L]、精子浓度[(16.89±1.17)×106/ml vs(12.75±1.02)×106/ml]以及精子活动率[(72.75±1.25)%vs(50.52±1.37)%]下降程度均明显减弱(P<0.05),而CMTM2+CP组的StAR蛋白表达水平则较高(1.16±0.07 vs 0.69±0.08,P<0.05)。结论:CMTM2可能通过调节StAR蛋白表达对抗CP引起的生殖毒性,从而在生殖系统中发挥一定的保护作用。Objective： To observe the effects of CMTM2 on cyclophosphamide （CP）-induced reproductive toxicity and the expression of steroidogenic acute regulatory （STAR） protein in the transgenic mouse model. Methods： Twenty CMTM2 transgenic mice were equally divided into a CMTM2 ＋ CP and a CMTM2 ＋ NS group, the former intraperitoneally injected with CP at 50 mg per kg per d, while the latter with the equivalent dose of normal saline, both for 7 days. Another 20 wild C57BL/6J mice were randomly assigned to a WT ＋ CF and a WT ＋ NS group, treated the same way above. After 30 days, all the mice were sacrificed and their epididymides and testes removed for measurement of the serum testosterone level by radioimmunoassay, determination of sperm concentration and mo-tihty by light microscopy and detection of the expression of StAR by Western blot. Results ： The levels of serum testosterone, sperm concentration and sperm motility were significantly decreased in the CMTM2 ＋ CP group as compared with the CMTM2 ＋ NS group （ [ 42.98 ± 3.25 ] nmol/L vs [ 46.74 ± 3.38 ] nmol/L, [ 16.89 ± 1.17 ] 106/ml vs [ 24.68 ±0. 95 ] x 10^6/ml, [ 72.75 ±1.25 ] % vs [ 85.14 ± 1.12 ] %, P 〈 0.05 ）, but remarkably less than in the WT ＋ CP group （ [ 37.97 ± 4.17 ] nmol/L, [ 12.75 ± 1.02 ] x 106/ml, [ 50.52 ± 1.37 % ） （ P 〈 0.05 ）. However, the expression of StAR was significantly higher in the CMTM2 ＋ CP than in the WT ＋ CP group （ 1.16 ± 0.07 vs0. 69 ± 0.08, P 〈 0.05 ）. Conclusion ： CMTM2 antagonizes cyclophosphamide-induced reproductive toxicity via regulating the expression of STAR, and hence plays a protective role in the reproductive system. Natl J Androl, 2#13, 19 （3） ： 210 -213

关 键 词：CMTM2 转基因小鼠 环磷酰胺 STAR 睾酮 精液 

分 类 号：R965[医药卫生—药理学]