S1P致环磷酰胺染毒后雄性小鼠凋亡蛋白表达的影响

Effects of S1P on the apoptins of male mice against the toxicity of cyclophosphamide

目的探讨1-磷酸鞘氨醇(S1P)对雄性小鼠生殖细胞毒性损害的拮抗机制。方法健康雄性昆明小鼠40只,随机分为5组,即正常对照组;S1P低剂量(0.5μg/10g小鼠体质量)、中剂量(1.0μg/10g小鼠体质量)、高剂量(2.0μg/10g小鼠体质量)组;环磷酰胺染毒组。腹腔注射给药5d,于首次给药后30d处死。分别采集睾丸样本,小鼠睾丸病理切片观察睾丸组织的病理学改变,免疫组化检测小鼠睾丸凋亡蛋白Bcl-2、Bax、Caspase-3的表达。结果与环磷酰胺染毒组相比:各S1P剂量组病理学结构均有不同程度的改善,Bcl-2蛋白表达增强,Bax、Caspase-3蛋白表达减弱。经图像分析软件分析后得出平均光密度值,各实验组与染毒组相比差异有统计学意义(P<0.05)。结论 S1P对雄性小鼠生殖细胞毒性损害具有一定的拮抗作用,可能通过活化Bcl-2和抑制Bax,抑制下游Caspase-3的表达来拮抗环磷酰胺所致的生殖毒性。

Objective To study the protective effects of S1P on male mouse reproductive cells by toxicity damage. Methods Forty healthy male Kunming mice were randomly divided into 5 groups （the physiological saline negative control group, the low,middle and high dose group of S1P（0.5, 1.0, 2.0 μg/10g）, the eyclophosphamide positive control group）. Mice in each group were given intraperitoneal injection for 5 days. The mice were killed at the thir- tieth day after the first treatment. Testis of the mice was collected and observed pathologic changes of testis by pathological section. And was detected Bcl-2, Bax, Caspase-3 expression by immunehistochemical staining. Results Compared with the positive control group, there were statistical significantly differences in the pathologic changes. The expression of Bcl-2 was improved and the expression of Bax,Caspase-3 were opposite （P〈0.05）. Conclusion There were some protective effects of S1P on male mouse reproductive cells by toxicity damage. Maybe the mecha- nism is S1P can inhibit apoptosis protein Bax and excited Bcl-2 to reduce the damage by toxicity.