棉酚对糖尿病大鼠肾脏转化生长因子β1和纤维连接蛋白及11β类固醇脱氢酶表达的影响  

The effects of gossypol on expressions of transforming growth factor-β1, fibronectin and 11β hydroxysteroid dehydrogenase in nephridial tissue in rats with diabetes mellitus

作　　者：陈三妹[1] 王蓉蓉[2] 王文艳[2] 吴晓烨[2] 陈国荣[2] 

机构地区：[1]绍兴文理学院医学院护理系,312000 [2]温州医学院附属第一医院病理科

出　　处：《中华老年医学杂志》2009年第6期496-499,共4页Chinese Journal of Geriatrics

基　　金：浙江省科技攻关项目（2007C34003）

摘　　要：目的观察棉酚对2型糖尿病大鼠肾脏病理变化影响，并探讨其作用机制。方法雄性SD大鼠随机分成正常组、糖尿肾病组及棉酚干预组。检测各组的血糖、胆固醇、低密度脂蛋白胆固醇水平；用光镜及电镜观察大鼠肾脏的组织形态学改变；反转录聚合酶链反应（RT—PCR）法检测肾脏组织转化生长因子β1（TGF-β1）、纤维连接蛋白（FN）、11β类固醇脱氢酶（11β-HSD1）、11βHSD2mRNA含量；免疫组织化学法测定大鼠。肾脏TGF—β1、FN表达水平。结果糖尿病组大鼠血糖、胆固醇、血低密度脂蛋白胆固醇水平高于正常组（P〈0．01），肾小球体积增大，肾小球毛细血管基底膜不规则增厚，足细胞突起、肿胀，可见足突融合，阳性基质增多，肾组织TGFβ1、FN基因mRNA表达及蛋白表达高于正常组（P〈0．01），1β-HSD2mRNA表达低于正常组（P〈0．05）；棉酚干预组血糖低于糖尿病组（P〈0．01），血胆固醇、低密度脂蛋白胆固醇水平有下降趋势；肾脏组织病理改变减轻，TGF—β1、FNmRNA表达及蛋白低于糖尿病组（0．16±0．02、0．22±0．05和0．24±0．06、0．33±0．07，P〈0．05），11β-HSD1、1β—HSD2mRNA表达与糖尿病组比较无明显改变。结论棉酚可改善2型糖尿病大鼠肾脏的病理改变，其作用机制与降血糖，进而抑制糖尿病大鼠肾脏TGF—β1、FN表达，阻止细胞外基质的堆积有关。Objective To observe the effects of gossypol on expressions of transforming growth factor-β1 （ TGF β1 ）, fibronectin （ FN ） and 11β-bydroxysteroid dehydrogenase （11β-HSD） in nephridial tissue in rats with diabetes mellitus. Methods Thirty male Sprague-Dawley rats were randomly divided into three groups： normal control, type 2 diabetes and gossypol treatment group . After high-fat feeding for 4 weeks, the later two groups were injected with low dosage strepozotocin （30 mg/kg） intraperitoneally to induce type 2 diabetic rat model. The rats in gossypol treated group were given gossypol at the dosage of 15 mg/kg once per day for 4 weeks by gavage. And since the 5th week, the times of garages had been changed into once per week at the same dosage and lasted to the 12th week. The levels of blood glucose, total cholesterol （TC）, low density lipoprotein-eholesterol （LDL-c） were measured. Additionally, the morphological changes of the kidney were studied by light microscopy and transmission electron microscopy respectively. The mRNA expressions of TGF-β1, FN, 11β-HSD and 11β-HSD2 in nephridial tissue were assayed by semi-quantity RT-PCR. The protein expressions of TGF-β1 and FN in nephridial tissue were determined by imrnunohistochemistry. Results The blood levels of glucose, TC and LDL c were increased significantly in type 2 diabetic group compared with normal control group（P〈0.01）. The volume of glomerulus and the deposition of PAS positive substance in the glomerular interstitium were increased under light microscopy, and the glomerular basal membrane was thicker in type 2 diabetic group than those in normal control group under transmission electron microscopy. The mRNA and protein expressions of TGF β1 and FN were increased（P〈0.01）, and the mRNA expression of 11β-HSD2 was decreased（P〈0.05）, while the mRNA expression of 11β-HSD1 was unchanged in type 2 diabetic group compared with normal control group. After the treatment of gossypol, the level of the blood glucos

关 键 词：糖尿病肾病 棉酚 11-β羟甾脱氢酶类 

分 类 号：R686[医药卫生—骨科学]