丝胶预处理对DN大鼠肾脏细胞外基质相关蛋白表达的影响  

Effects of Sericin Pretreatment on the Expression of ECM Associated Protein in the Kidney of Diabetic Nephropathy Rats

作　　者：陈志宏[1] 宋成军[1] 付秀美[1] 付文亮[1] 薛景凤[1] 

机构地区：[1]承德医学院基础医学部解剖学教研室,河北承德067000

出　　处：《中国医科大学学报》2010年第2期112-115,共4页Journal of China Medical University

基　　金：河北省教育厅项目(2006301);河北省科技厅项目(08276101D-19)

摘　　要：目的探讨彩色蚕茧提取物—丝胶预处理对糖尿病肾病(DN)大鼠肾脏细胞外基质(ECM)相关蛋白表达的影响。方法36只雄性SD大鼠随机分为3组(每组12只):正常对照组、DN模型组和丝胶预防组。模型组、丝胶预防组大鼠均建立链脲佐菌素(STZ)致动物模型,以血糖≥16.7mmol/L为成模标准;丝胶预防组大鼠于注射STZ前给与丝胶(2.4g·kg-1·d-1)灌胃35d。采用酶法检测血糖,ELISA方法检测血清Ⅳ型胶原(cⅣ)和层黏蛋白(LN)的含量;免疫组化染色观察肾脏转化生长因子-β1(TGF-β1)和基质金属蛋白酶组织抑制因子-1(TIMP-1)蛋白的表达;Westernblot法观察肾脏Smad3蛋白的表达。结果与正常对照组大鼠相比,模型组大鼠血糖,血清cⅣ和LN含量,肾脏TGF-β1、TIMP-1和Smad3蛋白的表达均明显升高(P<0.01)。丝胶预防组大鼠的血糖、血清cⅣ和LN含量,肾脏TGF-β1、TIMP-1和Smad3蛋白的表达明显低于模型组(P<0.01)。结论丝胶预处理可抑制DN肾脏中TGF-β1/Smad3信号通路的激活,防止TIMP-1蛋白高表达导致的MMPs活性的降低,从而预防DN时ECM的积聚和肾小球硬化,对DN的发生发展具有良好的预防作用。Objective To investigate the effects of sericin pretreatment on the expression of extracellular matrix （ECM） associated protein in diabetic nephropathy （DN） rats＇ kidney. Methods Sixty six male SD rats were randomly divided into 3 groups （n=12）：nonnal control group, DN model group and serieine prelreatment group. DN rats model in model group and sericine pretreatment group were established by intraperitoneally injection of streptozotocin （STZ）. Blood glucoses〉 16.7 mmol/L was taken as the standard of successful modelization. The rats in sericine pretreatment group were lavaged with serieine （2.4 g·kg^-1·d^-1） for 35 days before injecting STZ. The enzymic method was used to measure the blood glucose. Type IV collagen （e IV ） and laminin （LN） content in the serum were detected by ELISA. The expression of transforming growth factor-β1 （TGF- β1） and tissue inhibitors of maprix metallopmteinase-1 （TIMP-1） protein in the kidney was ob- served by immunohistochemieal staining. The expression of Smad 3 protein in the kidney was detected by Western blot. Results Compared with normal control rats,the blood glucose,eIV and LN content in the serum,TGF-β1,TIMP-1 and Smad 3 expression in the kidney of the model group rats increased obviously （P 〈 0.01 ）. The blood glucose,cIW and LN content in the serum, TGF-β1, TIMP-1 and Smad3 expression in the kidney of rats in sericine pretreatment group were significantly lower than those of the rats in model group （P 〈 0.01 ）. Conclusion Seriein pretreatment can inhibit the activation of TGF-β1/Smad 3 signal pathway in the kidney of DN rats,and prevent the decrease of MMPs activity induced by up-regulation of TIMP-1. So sericin can prevent accumulation of ECM and glomemloselerosis during DN, and has satisfactory apotropaic effects on the development of DN.

关 键 词：丝胶 预处理 糖尿病肾病 细胞外基质 转化生长因子-β1 SMAD3 基质金属蛋白酶组织抑制因子-1 

分 类 号：R587.1[医药卫生—内分泌]