桑酮碱对2型糖尿病肾病大鼠的保护作用及机制  

Effect of Sangtongjian mixture on rats with type 2 diabetic nephropathy

作　　者：马志[1] 孟庆海[1] 蒯美玉 林超[1] 张亚云[1] 孙鑫[1] 姚远[1] 张启春[1,2] 卞慧敏[1,2] 

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中药药效与安全性评价重点实验室,江苏南京210023

出　　处：《中成药》2016年第6期1215-1220,共6页Chinese Traditional Patent Medicine

基　　金：江苏高校优势学科建设工程资助项目(PAPD);国家自然科学基金(81072985;81573529)

摘　　要：目的观察桑酮碱(桑叶总黄酮和总生物碱)对2型糖尿病肾病大鼠的肾功能和肾TGF-β1/Smad信号通路的影响。方法以高脂联合链脲佐菌素复制2型糖尿病肾病大鼠模型,成模后分为模型组,二甲双胍组,桑酮碱低、中、高剂量组,另设正常空白组10只。灌胃给药,12周后测定各组大鼠空腹血糖及24 h尿量,尿液中白蛋白、肌酐的含有量;取血测定血清肌酐、尿素氮,并计算肌酐清除率;HE染色观察肾脏形态学的变化;Western bolt方法测定TGF-β1、Smad2/3、p-Smad2/3、IV型胶原(Co IV)、E钙黏蛋白(E-Ca)的蛋白表达水平;real time PCR方法检测Tgfb1、Co IV和E-Ca的mRNA表达水平。结果桑酮碱给药组能够显著降低糖尿病肾病大鼠空腹血糖、24 h尿量、尿白蛋白含有量及肌酐清除率,改善肾脏组织病理损伤,下调TGF-β1、p-Smad2/3、Co IV的表达,上调E-Ca表达。结论桑酮碱能延缓2型糖尿病大鼠早期肾病并发症的发生,其机制与调节肾脏TGF-β1/Smad信号通路有关。AIM To observe the effect of Sangtongjian mixture（total flavones and alkaloids from Morus alba）on rats with type 2 diabetic nephropathy（DN） and on TGF-β1/Smad pathway and its mechanism of action.METHODS SD rats induced by the combination of STZ and high fat diet were established as the DN model.The DN rats were divided into model group,metformin group,low-,middle-,and high-dose Sangtongjian mixture groups.Ten normal rats were set as the control group.Each treatment group was orally given the corresponding agents for twelve weeks.The levels of fasting blood glucose,24 h urine volume,urinary albumin,urine creatinine were measured after treatments.Histopathology changes of kidney were evaluated by HE staining.Protein levels of TGF-β1,Smad2/3,p-Smad2/3,Co IV,and E-Ca were determined by Western blot;mRNA levels of Tgfb1、Co IV,E-Ca were evaluated by real time PCR.RESULTS Sangtongjian mixture group could remarkably reduce the levels of fasting blood glucose,24 h urine volume,urinary albumin,and urine creatinine.Furthermore,Sangtongjian mixture could also attenuate the pathological changes of kidney,down-regulate the expression of TGF-β1,p-Smad2/3,Co IV and up-regulate the expression of E-Ca.CONCLUSION Sangtongjian mixture can delay the progression of early 2 type DN,and their mechanism of action might be associated with the regulation of TGF-β1/Smad pathway in kidney.

关 键 词：桑酮碱 糖尿病肾病 肾小球滤过率 TGF-β1/Smad通路 

分 类 号：R966[医药卫生—药理学]