中药复方糖耐康对KKAy小鼠肾小管上皮细胞转分化的影响  

Effect of Tang-Nai-Kang on Trans-differentiation of Renal Tubular Epithelial Cell in KKAy Mice

作　　者：吴丽丽[1] 刘铜华[2] 孙文[3] 周静鑫[4] 秦灵灵[5] 李佳[4] 郭璇[4] 穆晓红[6] 杨丽霞[7] 

机构地区：[1]北京中医药大学中医养生学研究所,北京100029 [2]北京中医药大学研究生院,北京100029 [3]北京中医药大学教育部中医养生学重点实验室,北京100029 [4]北京中医药大学东方医院,北京100078 [5]北京中医药大学科技处,北京100029 [6]北京中医药大学东直门医院,北京100700 [7]甘肃省中医药研究院,兰州730050

出　　处：《世界科学技术-中医药现代化》2014年第5期1035-1041,共7页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委面上项目(30973909):糖耐康干预糖尿病小鼠肾小管上皮细胞转分化研究;负责人:刘铜华;北京中医药大学创新团队项目(2011-CXTD-19):中医药防治糖尿病研究团队;负责人:刘铜华;教育部中医养生学重点实验室(201212);负责人:刘铜华;北京市科委中医养生学重点实验室(BZ0259);负责人:刘铜华;北京中医药大学青年教师专项计划:匙羹藤酸干预胰岛β细胞凋亡作用机制研究;负责人:吴丽丽

摘　　要：目的:探讨中药复方糖耐康对KKAy小鼠肾小管上皮细胞转分化的影响及其可能机制。方法:12周龄雄性KKAy小鼠50只,按血糖随机分为模型组、缬沙坦组、糖耐康高、中、低剂量组,每组10只,另设10只C57BL/6J小鼠为正常组,正常组和模型组给予0.9%氯化钠溶液,其余组给予对应浓度的药液灌胃,用药8周后处死,取肾脏组织,进行Mosson、PAS染色,免疫组化染色观察平滑肌肌动蛋白(α-SMA),E-钙黏蛋白(E-cadherin)的表达分布;Western Blot检测转化生长因子-β1(TGF-β1)表达。结果:与正常组相比较,模型组小鼠肾纤维化面积显著增大(P<0.01),α-SMA蛋白表达呈现较强阳性,E-cadherin蛋白表达弱阳性。与模型组比较,缬沙坦组、糖耐康各剂量组肾纤维化面积显著减小(P<0.01),α-SMA蛋白表达显著减少(P<0.01),而E-cadherin蛋白表达明显增加(P<0.05)。KKAy小鼠肾脏组织TGF-β1蛋白表达较正常小鼠显著升高(P<0.01);与模型组比较,缬沙坦组、糖耐康低、中和高剂量组TGF-β1蛋白表达含量都显著降低(P<0.01),其中糖耐康高剂量组与缬沙坦组相比较TGF-β1显著降低。结论:中药复方糖耐康可抑制肾小管上皮细胞EMT的发生,减轻肾小管间质纤维化而发挥肾脏保护作用。This study was aimed to explore the effect of Tang-Nai-Kang （TNK） on trans-differentiation of renal tubular epithelial cell in KKAy mice in order to discuss the possible mechanism. Fifty 12-week-old male KKAy mice were randomly divided into the model group, valsartan group, TNK high-dose, middle-dose and low-dose group, with 10 rats in each group. Ten C57BL/6J mice were used in the normal group. Rats in the model group and normal group were given 0.9% sodium chloride solution. Rats in other groups were given the corresponding drugs. After 8 weeks of gavage administration, kidneys of all mice were sampled and given Mosson and PAS dyeing. Expression distribution of α-smooth muscle actin （α-SMA） and E-cadherin in kidney tissues were observed under immunohistochemical staining. Expression of transforming growth factor-β1 （TGF-β1） was measured by western blot. The results showed that compared with the normal group, the area of renal fibrosis in the model group was significantly increased （P 〈 0.01）; the expression of α-SMA was stronger; and the expression of E-cadherin was weaker. Compared with the model group, the area of renal fibrosis in the valsartan group, TNK high-dose, middle-dose and low-dose groups were significantly decreased （P〈 0.01）; the expression of α-SMA was weaker （P〈 0.01）;and the expression of E-cadherin was obviously increased （P 〈 0.05）. The TGF-β1 expression in the model group was significantly higher than that in the normal group （P 〈 0.01）. Compared with the model group, the TGF-β1 expression in the valsartan group, TNK low-dose, middle-dose and high-dose groups were significantly lowered （P〈0.01）. And the TGF-β1 expression in the TNK high-dose group was even lower than that in the valsartan group. It was concluded that TNK was able to suppress the epithelial-mesenchymal transition （EMT） of renal tubular epithelial cell, and lessen the renal tubule interstitial fibrosis, in order to protect the kidney.

关 键 词：糖耐康 KKAY小鼠 肾小管上皮细胞转分化 肾脏保护 

分 类 号：R285.5[医药卫生—中药学]