糖尿病大鼠肾脏XBP1的表达及普罗布考的干预研究

Expression of XBP1 in the kidney of diabetic rats and the protective effect of probucol

目的通过观察糖尿病大鼠肾脏中X盒结合蛋白1(XBP1)的表达,评价肾脏的内质网应激水平,并通过观察普罗布考对XBP1表达的影响,探讨其肾脏保护作用。方法 80只大鼠随机分为健康对照组(C组n=25)及造模组(n=55),造模组给予链脲佐菌素(STZ)60mg/kg一次性腹腔注射构建1型糖尿病大鼠模型,将造模成功的糖尿病大鼠随机分为糖尿病组(D组n=28),普罗布考组(P组n=27)。P组给予普罗布考110mg/kg.d灌胃,D组及C组给予同体积蒸馏水灌胃。分别检测4周,8周及12周24h尿蛋白,血清胆固醇、甘油三脂、尿素氮及肌酐。光镜下观察肾脏病理变化,免疫组化观察肾组织XBP1的表达情况,western-blot测定XBP1的表达情况。结果 C组24h尿蛋白、血清尿素氮、肌酐、甘油三酯及胆固醇4周,8周及12周均处于正常范围,D组以上指标在4周、8周及12周逐渐升高,明显高于同时间的C组,差别有统计学意义(P<0.05),P组以上指标亦逐渐升高,但明显低于同时间的D组,差别有统计学意义(P<0.05);C组大鼠肾脏在4周、8周及12周均显示正常肾脏结构,D组大鼠表现出明显的节段性硬化等糖尿病肾病的病理改变,P组大鼠病理改变较D组明显减轻;免疫组化显示D组大鼠肾脏中XBP1的表达在4周、8周及12周逐渐升高,明显高于同时间C组,P组大鼠肾脏中XBP1的表达较D组明显减少,免疫组化积分均有统计学差异(P<0.05);Westernblot结果与免疫组化相符。结论糖尿病大鼠肾脏中XBP1的表达增多,说明糖尿病大鼠肾脏中内质网应激水平升高,普罗布考可以通过降低内质网应激,下调XBP1的表达起到肾脏保护作用。

Objective To investigate the expression of 4-HNE in the kidney of diabetic rats and the protective effect of probucal.Methods 80 rats were randomly divided into three groups：control group（group C）,diabetic group（group D）and probucol treated group（group P）,group D and group P were giwen STZ（60mg/kg）by intraperitoneal injection to establish rat model of diabetic.After rat model of diabetic succesfully established,rats in group P were treated by probukol（110mg/kg.d）,rats in group D and group C were given equal volume water insdead.SCr、BUN、TG、TC and urinary protein were measured at the4th、8th and 12 th weeks.HE staining were used to evaluate the pathological change of the kidney.The immunohistochemistry and Western-blot were used to detect the expression of XBP1 in renal tissue.Results The serum creatinine、BUN、TG、TC and24-hour urinary protein in group D and grou P were increased in 4th、8th and 12 th weeks,and were higher than those in group C（P〈0.05）.The pathological changes of the kidney in group D were more serious than group P.The expression of XBP1 in group P was significantly lower than group D,（P〈0.05）,but was much higher than group C（P〈0.05）.Conclusion The XBP1 expression siginificantly increases in the kidney of STZ induced diabetic rats,Probucol can protects the diabetic kidney through decreasing the expression of XBP1 and the leval of endoplasmic reticulumStress.