目的探讨锌对砷致大鼠睾丸损伤中相关保护作用的机制,为预防砷的生殖毒性及辅助性治疗提供理论依据。方法清洁级SD雄性大鼠30只,体重200 g左右,随机分为3组,分别为对照组(蒸馏水)、砷组和砷+锌组。对照组、砷组分别给亚砷酸钠0 mg/L、60 mg/L,砷加锌组每日分别予浓度为60 mg/L As(As为亚砷酸钠)+227 mg/L Zn(Zn为硫酸锌)的水溶液,采用自由饮水方式进行染毒,连续染毒12周,每天称体重。染毒结束后处死大鼠,摘取睾丸组织、称重;分光光度法检测睾丸组织匀浆中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)及丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮合酶(NOS)的活力及一氧化氮(NO)的含量。光镜下观察睾丸形态变化,实时荧光定量聚合酶链反应(Real-Time PCR)测定各组大鼠睾丸的金属硫蛋白-1(MT-1)、金属硫蛋白-2(MT-2)基因表达情况。结果 HE染色结果显示,对照组大鼠睾丸结构可见精子发育良好、生精上皮细胞排列有序,睾丸间质中血管完整。砷组大鼠睾丸,可见其生精小管中生精上皮坏死及空泡化,睾丸间质水肿、坏死出血。锌+砷组大鼠睾丸一些生精小管中逐渐出现正常组织结构。与对照组比较,砷组睾丸MDA含量显著增加(P<0.01);砷+锌组睾丸MDA浓度显著低于砷组(P<0.01)。与对照组比较,砷组睾丸SOD活力显著降低(P<0.01);砷+锌组中睾丸SOD活力显著高于砷组(P<0.01)和对照组(P<0.05)。与对照组比较,砷组睾丸GSH-Px的活力显著下降(P<0.01);与砷组比较,砷+锌组睾丸GSH-Px活力升高(P<0.01)。与对照组比较,砷组睾丸CAT的活力显著下降(P<0.01);与砷组比较,砷+锌组睾丸CAT活力升高(P<0.01),与对照组比较,砷组NOS活性显著性降低(P<0.01)。与对照组比较,砷组睾丸MT-1、MT-2基因表达水平明显上调了3.60倍和1.90倍;而砷+锌组与对照组比较,大鼠睾丸MT-1表达水平也上调2.04倍,MT-2没有明显的变化;但砷+锌组与砷组比较,砷+锌组MT-1、MT-2基因表达明显下调(P<0.01)。结论 1.亚慢性砷中毒可增强睾丸组织氧化应激效应,导致大鼠睾丸MT-1、MT-2基因表达上调;而砷暴露的同时补锌,其MT-1、MT-2基因表达下调。2.补锌后机体可能通过调节MT-1、MT-2基因表达,改善睾丸的抗氧化状态等机制,阻止砷的积累和锌的耗损,从而缓解大鼠砷暴露所致的睾丸损伤。 Objective To explore the mechanism of zinc-induced arsenic-induced injury in testis of rats and provide a theoretical basis for the prevention of arsenic toxicity and adjuvant therapy. Methods Thirty male Sprague-Dawley rats weighing 200 g were randomly divided into three groups: control group (distilled water), arsenic group and arsenic + zinc group. The concentrations of arsenic and sodium arsenite in the control and arsenic groups were 60 mg / L and 60 mg / L, respectively (As for sodium arsenite) +227 mg / L Zn (Zn zinc sulfate) aqueous solution, using free drinking water for exposure, continuous exposure for 12 weeks, weighing each day. The rats were sacrificed after the exposure and the testicular tissues were harvested and weighed. The contents of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in the testis homogenate were measured by spectrophotometry. (GSH-Px), nitric oxide synthase (NOS) and the content of nitric oxide (NO). The morphological changes of testis were observed under light microscope. The contents of MT-1 and MT-2 in testis were determined by real-time PCR. Express the situation. Results The results of HE staining showed that the spermatozoa were well developed in testicular structure of rats in the control group, the germ cells were arranged in order, and the blood vessels were intact in the testicular stroma. Arsenic rats testicles, showing the seminiferous tubules in the seminiferous epithelium necrosis and vacuolization, testicular interstitial edema, necrosis bleeding. Zinc + arsenic rats testicular germ tube some gradual emergence of normal tissue structure. Compared with the control group, the content of MDA in testes of arsenic group increased significantly (P <0.01), and the content of MDA in testes of arsenic + zinc group was significantly lower than that of arsenic group (P <0.01). Compared with the control group, SOD activity in testes of arsenic group was significantly lower (P <0.01); SOD activity in testes of arsenic + zinc group was significantly higher than that of arsenic group (P <0.01) and control group (P <0.05). Compared with the control group, GSH-Px activity in testes of arsenic group was significantly decreased (P <0.01). Compared with arsenic group, GSH-Px activity in testes of arsenic + zinc group was increased (P <0.01). Compared with the control group, the activity of CAT in the arsenic group was significantly decreased (P <0.01). Compared with the arsenic group, the CAT activity in the arsenic + zinc group was significantly increased (P <0.01). Compared with the control group, Decreased (P <0.01). Compared with the control group, the expression of MT-1 and MT-2 in testes of arsenic group was significantly increased by 3.60-fold and 1.90-fold, while the level of MT-1 in testes of arsenic + zinc group was also increased by 2.04 fold compared with the control group The MT-2 and MT-2 mRNA expressions in arsenic and zinc groups were significantly decreased (P <0.01). Subchronic arsenic poisoning can increase the oxidative stress in testis tissue and lead to the up-regulation of MT-1 and MT-2 gene expression in rat testes; while the exposure to arsenic and the zinc supplementation, the MT-1 and MT-2 gene expression are down-regulated . After zinc supplementation, the body may alleviate the testicular damage caused by exposure to arsenic in rats through mechanisms such as regulating MT-1 and MT-2 gene expression and improving the antioxidant status of the testis to prevent arsenic accumulation and zinc depletion.