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观察金雀异黄酮(genistein)替代治疗对卵巢切除大鼠心肌中一氧化氮(nitricoxide,NO)和内皮型一氧化氮合酶(endothelialnitricoxidesynthase,eNOS)的影响。成年雌性Sprague-Dawley大鼠经双侧卵巢切除术,假手术组作为对照,术后三周将行卵巢切除术的大鼠随机分为低剂量genistein(0.5mg/kg·d-1)、高剂量genistein(5.0mg/kg·d-1)、17-β雌二醇(0.1mg/kg·d-1)和模型组(100μl/d芝麻油),各组均皮下注射给药并给予不含大豆的饲料喂养6周,测定大鼠尾动脉血压、心率,麻醉后放血处死大鼠称量子宫重量;放免法检测血浆中总雌二醇,亚硝酸还原酶法检测心肌匀浆中NO,Westernblot检测心肌中eNOS的表达以及eNOS的调节蛋白小凹蛋白-1(caveolin-1)和钙调素(calmodulin)的表达情况。结果显示各组间大鼠血压无显著性差异,同17-β雌二醇一样,genistein能呈剂量依赖性地增加心肌组织中eNOS表达量和NO生成,同时genistein能明显降低内源性eNOS活性抑制物caveolin-1的表达,而不影响eNOS活性正性调节蛋白钙调素的表达。与溶媒对照组比较,0.5mg/kg·d-1的genistein不增加子宫重量,5.0mg/kg·d-1的genistein增加子宫重量3倍,但较17-β雌二醇(增加6倍)的作用小(P<0.01)。上述结果提示,植物雌激素genistein剂量依赖性地上调心肌组织eNOS的活性并增加NO的生成,减少抑制eNOS活性的小凹蛋白-1表达。
To observe the effects of genistein replacement therapy on nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) in ovariectomized rats. Adult female Sprague-Dawley rats were subjected to bilateral ovariectomy and sham-operated group as controls. After three weeks, ovariectomized rats were randomly divided into low-dose genistein (0.5 mg/kg·d-1) and high doses. Dose of genistein (5.0 mg/kg·d-1), 17-β estradiol (0.1 mg/kg·d-1) and model group (100 μl/d sesame oil), each group was administered subcutaneously and given without Soybean feed was fed for 6 weeks. The blood pressure and heart rate of the tail artery were measured. The uterine weight was weighed after exsanguination. The plasma total estradiol was measured by radioimmunoassay, and the NO in myocardial homogenate was detected by nitrite reductase method. Western blot The expression of eNOS and the expression of caveolin-1 and calmodulin, the eNOS regulatory proteins, were detected in myocardium. The results showed no significant differences in blood pressure between the groups. Similar to 17-beta estradiol, genistein dose-dependently increased eNOS expression and NO production in the myocardium, while genistein significantly reduced endogenous eNOS activity. Inhibitor caveolin-1 expression without affecting eNOS activity positive regulatory protein calmodulin expression. Compared with the vehicle control group, genistein 0.5 mg/kg d-1 did not increase uterine weight, genistein 5.0 mg/kg d-1 increased uterine weight 3 times, but compared to 17-beta estradiol (6 fold increase) The effect was small (P<0.01). The above results suggest that phytoestrogen genistein dose-dependently up-regulates the activity of eNOS in myocardial tissue and increases the production of NO, and decreases the expression of paroxysin-1 that inhibits the activity of eNOS.