镉对去卵巢大鼠肾脏的类雌激素作用

Estrogen-mimicking effects of cadmium on kidneys of ovariectomized rats

目的观察镉染毒对去卵巢大鼠肾脏中雌激素受体α(ERα)、雌激素受体β(ERβ)表达的影响。方法将24只健康12周龄SPF级SD雌性大鼠随机分为3组,分别为假手术(蒸馏水)组、去卵巢(蒸馏水)组、染镉(200 mg/L)去卵巢组,每组8只。假手术组切除小块卵巢周围的脂肪,去卵巢组和染镉去卵巢组切除双侧卵巢。术后1周,采用自由饮水方式进行染毒,连续染毒12周。采用电感耦合等离子体质谱法测定大鼠血镉、尿镉水平,采用酶联免疫吸附测定血清雌二醇、β2-微球蛋白水平,采用Western blot技术检测肾脏组织中ERα、ERβ蛋白的表达水平。结果与假手术组相比,去卵巢组染镉组12周末体重下降(P<0.05)、肾脏系数升高(P<0.05),去卵巢组及染镉去卵巢组雌激素水平降低(P<0.05);与去卵巢组相比,染镉去卵巢组体重、雌激素水平降低(P<0.05),肾脏系数、β2-微球蛋白、尿镉及血镉水平升高(P<0.05);染镉去卵巢组血镉与尿镉、β2-微球蛋白、肾脏ERβ的表达水平正相关(P<0.05),而与ERα无统计学相关性(P>0.05)。结论重金属镉可降低去卵巢大鼠血清雌激素水平及增加雌激素受体β受体表达,这可能是镉的肾毒性作用机制之一。

Objective To clarify whether cadmium-induced nephrotoxicity is mediated via estrogen receptor α（ERα） or estrogen receptor β（ERβ） signaling. Methods A total of 24 SD female rats in SPF grade were randomly divided into three groups：sham- operated group（ treated with distilled water）, ovariectomized group（ treated with distilled water）, cadmium group（ovariectomized rats treated with Cd Cl2,200 mg/L）. One week after ovariectomization, continuous exposure to cadmium for 12 weeks was conducted through drinking water,kidney weight and histological examination,serum estradiol,serum β2-microglobulin levels,serum and urine cadmium,estrogen receptor alpha,estrogen receptor beta in kidney expression were investigated. Results Compared with sham-operated group,weight loss happened and kidney coefficient increased in cadmium group,serum estradiol were significantly decreased in ovariectomized group and cadmium group. Compared with ovariectomized group,serum estradiol decreased and kidney coefficient,β2-microglobulin,urinary cadmium and blood cadmium levels increased in cadmium group（P〈0.05）. Serum cadmium was positively correlated with urine cadmium,β2-microglobulin levels,ERβ expression in kidney,whereas no significant changes in ERα was observed in cadmium-exposed rats. Conclusion Serum estrogen levels decrease and estrogen receptor β receptor expression increase in ovariectomized rat may be involved in cadmium-induced kidney damage.