拉辛司克糖尿病肾病保护作用的分子机制  

Molecular mechanism of protective effect provided bylaxinskat on diabetic nephropathy

作　　者：叶皓[1] 阚启明[2] 匡亚飞[2] 张辉[1] 刘铮[2] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]沈阳药科大学生命科学学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2016年第7期560-564,571,共6页Journal of Shenyang Pharmaceutical University

基　　金：国家基础科学人才培养基金资助项目(J1103606)

摘　　要：目的考察醛糖还原酶抑制剂拉辛司克(laxinskat)治疗糖尿病肾病的作用及分子作用机制。方法采用KKAy小鼠给予高脂饲料制造小鼠糖尿病肾病模型,通过测定血清C反应蛋白CRP(c-reaction protein)含量和肾皮质醛糖还原酶AR(aldose reductase)活性考察拉辛司克对糖尿病肾病的保护作用及作用部位。采用体外高糖条件下培养大鼠肾小球系膜细胞制备糖尿病肾病细胞模型,采用MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)法考察拉辛司克抑制肾小球系膜细胞增生作用,并利用Western-Blot技术测定细胞内P21蛋白质含量,确定其分子机制。结果整体水平上拉辛司克,23 mg·kg^(-1)剂量能够明显减少糖尿病肾病模型小鼠CRP含量,降低肾皮质内AR含量,作用与依帕司他相当;细胞水平上拉辛司克,10、100μmol·L^(-1)能够增加肾小球系膜细胞肾小球系膜细胞内P21蛋白生成,抑制细胞生长,改善细胞增生肥大,作用强与依帕司他(epalrestat,EPAL)。结论拉辛司克(laxinskat)能够改善KKay糖尿病肾病模型小鼠肾病发展进程,其作用部位可能在肾脏皮质部;通过细胞模型研究确定其治疗糖尿病肾病的机制与促进肾小球系膜细胞P21蛋白生成从而抑制细胞生长有关,作用机制与依帕司他不完全相同。Objective To investigate the role and molecular mechanism of aldose reductase inhibitor laxinskat on diabetic nephropathy. Methods Toinvestigate the role and molecular mechanism of aldose reductase inhibitor laxinskaton diabetic nephropathy. Methods After the establishment of mouse diabetic nephropathy model by giving high fat diet to KKAy mice,the content of C-reactive protein（ CRP） in serum and the activity of cortical aldose reductase（ AR） were detected to investigatethe protective effect oflaxinskaton diabetic nephropathy and the site of action. Results On diabetic nephropathy mice models, laxinskat administered with the dose of 23 mg·kg^-1 can significantly reduce CRP level and renal cortex AR content,and the effect was comparable to Epalrestat. At cell level,laxinskat（ 10 or 100 μmol） could increase the expression of P21 protein,inhibit cell growth,and improve cell hypertrophy,and the effect is stronger thanthat of Epalrestat. Conclusions Laxinskat can ameliorate diabetic nephropathy development process in KKAy model mice,and its action site may be at kidney cortex. Laxinskat can improve diabetic nephropathy by stimulating P21 protein expression and therefore inhibit cell growth in cell model. The related mechanism is different from Eparestat.

关 键 词：醛糖还原酶抑制剂 拉辛司克 糖尿病肾病 肾小球系膜细胞 

分 类 号：R96[医药卫生—药理学]