GSK3β抑制剂对糖尿病肾病大鼠肾组织TGF-β1和血清PAI-1表达的影响  

The effects of GSk3β inhibitor on the expression of renal TGF-β1 and serum PAI-1 of rats with diabetic nephropathy

作　　者：周文华[1] 孔丽丽[1] 贾冶[1] 崔英春[1] 鲍妍[1] 刘声茂[1] 

机构地区：[1]吉林大学第二医院肾病内科,吉林长春130041

出　　处：《中国实验诊断学》2013年第4期634-639,共6页Chinese Journal of Laboratory Diagnosis

基　　金：吉林省卫生厅科研课题(2009Z073)

摘　　要：目的观察糖原合成酶激酶-3β(GSK3β)抑制剂Licl对糖尿病肾病(DN)大鼠的影响,从而明确GSK-3β抑制剂对DN的作用机制。方法将60只雄性Wistar大鼠随机分为四组:正常对照组(NC组,n=10),Licl组(n=10),DN组(n=20),DN+Licl组(n=20)。通过一次性腹腔注射链脲佐菌素(STZ)联合长期高脂饮食,建立DN大鼠模型;通过腹腔注射GSK-3β抑制剂Licl进行药物干预。观察各组大鼠一般状态、体重、肾重/体重的变化;检测血糖、尿量、尿蛋白、血肌酐等指标;肾脏PAS染色观察各组大鼠肾脏病理改变;ELISA方法检测各组大鼠血清纤溶酶原激活物抑制物-1(PAI-1)的水平,IHC方法检测肾组织转化生长因子-β1(TGF-β1)的表达,进行组间比较。结果与NC相比,DN组大鼠一般状态、体重、肾重/体重、血糖、血肌酐、尿量、尿蛋白、肾脏病理均出现了DN特有的变化特征,血清PAI-1明显增高,肾组织TGF-β1的表达明显上调。DN+Licl组较DN组大鼠存活率高,尿蛋白、血清PAI-1表达显著减少,肾脏病理较DN组明显减轻,而肾组织TGF-β1表达明显增加。结论 GSK-3β抑制剂Licl能够降低DN大鼠血清PAI-1水平、蛋白尿及死亡率。DN大鼠较正常大鼠肾组织TGF-β1表达明显上调,GSK-3β抑制剂Licl能进一步增加DN大鼠肾组织TGF-β1蛋白的表达。抑制GSK-3β,对治疗DN有积极的意义。但是GSK-3β抑制剂Licl作为药物治疗DN,应考虑其效应的两面性。Objective The purpose of this research is to observe the effects of Glycogen synthase kinase-3 beta （GSK-3 Beta） inhibitor Licl on rats with diabetic nephropathy（DN） in order to determine the effect of GSK--β3 inhibitor on DN and its mechanism. Methods 60 male Wistar rats were randomly divided into four groups.. Normal control group （NC group,n ~ 10） ,Licl group（n~ 10） ,DN group（n = 20） ,DN＋Licl group（n= 20）. The rat model of diabetic ne- phropathy was established by single intraperitorLeal injection of STZ and feeding on high fat diet. Drug intervention was implemented by intraperitoneal injection of GSk-313 inhibitor Licl. The changes in general state, weight, kidney weight/ body weight of rats in each group were observed;Indexes such as blood glucose, urine volume, urinary protein, serum creatinine were detected;Renal pathological changes of rats in each group were observed by PAS staining method. Ser- um PAI-1 of rats in each group was examined by enzyme-linked immunosorbent assay （ELISA） ,and expression of renal TGF--β1 was examined by immunohistochemisty（IHC）, and then inter-group comparisons were carried out. Results Compared with normal control group, general state, weight, kidney weight / body weight, blood glucose, serum creati- nine, urine volume, urinary protein~ renal pathology of rats in DN group appeared specific features of DN, serum PAI-1 increased significantly,expression of renal TGF-β1 was up-regulated significantly. Compared with DN group, survival rate of rats in DNq-Licl group was higher, urinary protein and Serum PAI-1 decreased significantly, renal pathology was alleviated notably,however,expression of renal TGF--β1 increased sharply. Conclusion GSK-3β inhibitor Licl can reduce serum PAI-1, proteinuria and mortality rate of rats with diabetic nephropathy. Compared with normal rats, expression of renal TGF-β1 of rats with diabetic nephropathy was significantly up-regulated. It can be futher increased by GSK-3β in- hibitor Licl. Inhibition of GSK-3β

关 键 词：糖原合成激酶-3β 糖尿病肾病 转化生长因子-Β1 纤溶酶原激活物抑制物-1 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]