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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。
AIM: To investigate whether CMTM2 can improve the reproductive toxicity caused by cyclophosphamide (CP) and its effect on the expression of StAR in the transgenic mouse model. Methods: Totally 20 CMTM2 transgenic mice were randomly divided into two groups: CMTM2 + CP [CMTM2 transgenic mice injected intraperitoneally with 50 mg / (kg.d) CP for 7 days and CMTM2 + NS (CMTM2 transgenic mice intraperitoneally The rats in the same group were injected with equal volume of saline for 7 consecutive days. Twenty (20) homozygous wild type C57BL / 6J mice were divided into two groups: WT + CP .d) CP] group and WT + NS (wild type C57BL / 6J mice were injected with an equal volume of saline for 7 consecutive days intraperitoneally). Thirty days later, the mice were sacrificed and sacrificed to detect the level of serum testosterone. The sperm concentration and sperm motility of mice in each group were analyzed. The expression of StAR protein in testis was detected by Western blotting. Results: Compared with CMTM2 + NS group, CP decreased serum testosterone level in CMTM2 + CP group (42.98 ± 3.25 nmol / L vs 46.74 ± 3.38 nmol / L) and sperm concentration (16.89 ± 1.17) × (72.75 ± 1.25)% vs (85.14 ± 1.12)%] (P <0.05), showing significant reproductive toxicity; compared with WT + CP (106 / ml vs 24.68 ± 0.95 × 106 / ml) (42.98 ± 3.25) nmol / L vs (37.97 ± 4.17) nmol / L] and sperm concentration [(16.89 ± 1.17) × 106 / ml vs (12.75 ± 1.02) × 106 / ml] and sperm motility [(72.75 ± 1.25)% vs (50.52 ± 1.37)%] (P <0.05), while the level of StAR protein in CMTM2 + CP group was higher vs 0.69 ± 0.08, P <0.05). Conclusion: CMTM2 may play a protective role in the reproductive system by regulating the expression of StAR protein against reproductive toxicity induced by CP.