锌调节类固醇激素合成蛋白的表达抑制邻苯二甲酸酯的睾丸毒性

Zinc inhibits phthalates-induced testicular toxicity by regulating the expression of steroidogenic proteins in mice

目的 研究锌抑制邻苯二甲酸酯类(phthalates, PEs)睾丸毒性的作用机制。方法 36只雄性ICR小鼠随机分对照组,邻苯二甲酸丁苄酯(butyl benzyl phthalate, BBP)、邻苯二甲酸正二丁酯[di(n-butyl) phthalate, DBP]和邻苯二甲酸二(2-乙基己基)酯[di(2-ethyhexyl) phthalate, DEHP]3种PEs等毒性混合物(MPEs)染毒组以及MPEs+Zn组。MPEs组小鼠灌胃160 mg/kg·d MPEs, MPEs+Zn组小鼠同时灌胃160 mg/kg·d MPEs和50 mg/kg·d ZnSO4。连续灌胃90 d,测定睾酮水平,并对睾丸进行组织病理学观察;Western blot检测睾丸组织中类固醇激素合成急性调节蛋白(StAR)和胆固醇侧链裂解酶(P450scc)、17α-羟化酶、C17,20裂解酶活性(CYP17A1)、17β-羟基类固醇脱氢酶(17β-HSD)、芳香化酶(P450arom)等蛋白表达水平。结果 MPEs组小鼠血清睾酮水平明显降低,差异有统计学意义(P<0.05),睾丸组织明显损伤,主要表现为曲细精管内精细胞排列紊乱、数量减少及发展停滞;与对照组相比,MPEs组睾丸组织StAR、P450scc、CYP17A1、17β-HSD和P450arom的表达水平升高(P<0.01);而MPEs+Zn组小鼠睾丸组织中这些指标较MPEs组均有明显的改善(P<0.05)。结论 锌能够抑制MPEs暴露所诱导的类固醇激素合成蛋白表达水平的改变,从而抑制其睾丸毒性。

Objective To study the mechanisms of zinc inhibiting phthalates-induced testicular toxicity in mice. Methods Thirty-six male ICR mice were randomly divided into control group, MPEs(the equipotent toxic mixture of butyl benzyl phthalate(BBP), di(n-butyl) phthalate(DBP) and di(2-ethyhexyl) phthalate(DEHP)) group, and MPEs+Zn group, with 12 mice in each group. Mice in MPEs group and MPEs+Zn group were treated with 160 mg/kg·d MPEs by gavage with or without 50 mg/kg·d ZnSO4. After intervention for 90 days, serum was collected for testosterone detection, then the mice were anesthetized and dissected, and the testes were collected for pathology observation. Western blot was performed to detect the expressions of testicular StAR, P450 scc, CYP17 A1, 17β-HSD and P450 arom. Results Serum testosterone was decreased in MPEs group(P<0.05), and the testicular tissue of mice in MPEs group was obviously damaged with disordered arrangement of the spermatids in the seminiferous tubule, as well as the spermatid count was decreased;and the spermatid development was arrested. Compared with control group, the expression levels of StAR, P450 scc, CYP17 A1, 17β-HSD and P450 arom were significantly increased in MPEs group(P<0.01). On the contrary, these parameters were significantly restored in MPEs+Zn group(P<0.05). Conclusion Zinc could inhibit the expression changes of steroidogenic proteins induced by MPEs, thereby inhibiting MPEs-induced testicular toxicity.