雌雄激素对去势雌鼠晶状体氧化代谢的影响

Effects of estrogen and androgen on lens oxidative damage after ovariectomy in rat

背景流行病学调查表明绝经期妇女白内障的发病率高于同龄男性，雌激素替代治疗可延缓白内障的发展，但雄激素在白内障发病中的作用尚不明确。目的研究雌雄激素对去势雌鼠晶状体抗氧化能力的影响。方法56只清洁级Wistar雌鼠随机分为正常对照组、假手术组、去势组、雌二醇点眼组、雌二醇注射组、睾丸酮点眼组、睾丸酮注射组，每组8只大鼠。除正常对照组及假手术组外，其余组雌鼠均行卵巢切除术，应用性激素大鼠于去势后5个月分别应用质量分数0．01％苯甲酸雌二醇注射液和2．5％丙酸睾丸酮点双眼及苯甲酸雌二醇注射液（200μg／kg）、丙酸睾丸酮（3．75mg／kg）肌内注射，共6周。假手术组仅切开腹腔后再缝合。用药后每周裂隙灯下观察大鼠晶状体混浊情况。分别于术前、术后5个月和用药后6周采集动物心脏血，评估大鼠血清中雌激素、雄激素质量浓度的变化，比较各组晶状体中超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、丙二醛（MDA）、水溶性蛋白（WSP）的含量。结果各组大鼠去势前后均未见到晶状体混浊。假手术组大鼠血清雌二醇质量浓度在手术前后及用药前后与正常对照组比较差异均无统计学意义（P〉0．05）。去势组和各用药组大鼠去势后5个月血清雌二醇质量浓度均明显低于正常对照组和假手术组（P〈0．01）。注射雌二醇、睾丸酮6周后大鼠血清雌二醇水平较同时间点去势组升高，差异均有统计学意义（P〈0．01）；雌二醇注射组大鼠晶状体SOD活性、晶状体中GSH和WSP水平雌二醇点眼组和去势组大鼠明显增加，而晶状体中的MDA水平明显下降，差异均有统计学意义（P〈0．01）；睾丸酮注射组晶状体中S01）活性和GSH水平较去势组下降，差异均有统计学意义（P〈0．05），而2组MDA、WSP水平差异均无统计学意义。结论雌激素可增强去势鼠晶状体的抗氧化能力，而雄激素可能加速去势雌鼠晶状体氧化损伤的发展。

Background Epidemiological investigation in human has been conclusive. In postmenopausal women, the incidence of cataract is higher than men at the same age. In addition, hormone replacement therapy may protect against the development of cataract. However,this role of androgen is not clear. Objective This study was to explore the effects of estrogen and androgen on anti-oxidative ability of lens after ovariectomy. Methods Fifty- six three-month-old clean female Wistar rats were randomly divided into normal control group,sham operation group, castration group,estrogen cyedrops group;estrogen injection group;androgen eyedrops group;androgen injection group and 8 rats for each. Ovariectomy was performed in the rats of castration group and gonadal hormone application group, and estradiol benzoate solution or testosterone propionate solution were utilized topically or systemly in 5 months after ovariectomy for 6 weeks respectively. Only abdominal cut was curried out in sham operation group. The lenses of rats were examined weekly under the slit lamp. The serum estrogen and androgen levels of rats were detected before, after operation and 6 weeks following the administration of gonadal hormone. The contents of superoxide dismutase（ SOD）, glutathione（GSH） ,malondialdehyde（MDA） and water-soluble protein（WSP） in rat lens homogenate were detected at the end of the experiment. Utilization of animals complied with the Regulation for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results No opacity of lenses was found during the experiment duration in various groups. The serum estradiol levels of rats in sham group were insignificantly different from normal groups in various time points （P〉0. 05 ）. The evident decline of serum estradiol was detected in the rats of castration group and gonadal hormone application groups compared with sham group in 5 months after operation （all P〈0. 01 ）. However,at the sixth weeks after the system use of estradiol or testosterone, the serum estradiol levels were significantly higher than the castration group and topical application groups of gonadal hormone（ P〈0. 01 ）. The contents of SOD ,GSH and WSP in lenses were considerably increased,but the MDA level in lenses was decreased after system use of estrogen（P〈0. 01）. The activity of SOD and GSH were lower after system use of testosterone in comparison with castration rats （P 〈 0.05 ）. Conclusion Estrogen can protect lens against oxidation damage. However, androgen, to a certain extent, may contribute to the development of oxidative damage in OVX female rats.