摘要
目的探讨西格列汀对糖尿病肾病大鼠肾脏c-Jun氨基末端激酶(JNK)信号通路的影响。方法40只清洁级健康雄性Wistar大鼠,按随机数字表法分为正常对照组(NC组)10只、糖尿病组(DM组)10只、西格列汀干预组1(ST1组,5 mg)10只、西格列汀干预组2(ST2组,10 mg)10只。实验周期16周。检测24 h尿微量白蛋白、尿素氮(BUN)、血肌酐(Scr),计算肌酐清除率(Ccr)。肾组织石蜡切片,苏木精-伊红(HE)染色观察肾组织病理形态学改变;免疫组织化学和实时聚合酶链反应(PCR)检测Nephrin及JNK相关蛋白c-Jun在肾脏的蛋白和基因表达。结果与DM组相比,ST1组与ST2组24 h尿微量白蛋白、血BUN、Scr均显著降低,肾组织病理损伤减轻,差异有统计学意义(P<0.05);与ST1组相比,ST2组上述指标变化更为明显。与DM组相比,ST1与ST2组Nephrin蛋白及基因表达增加,c-Jun蛋白及基因表达降低(P<0.05);ST2组较ST1组变化更为明显。结论西格列汀可能通过抑制糖尿病肾病大鼠肾脏JNK信号通路的活性,上调足细胞Nephrin的表达,产生有效的肾保护作用。
Objective To investigate the effect of sitagliptin on c-Jun N-terminal kinase（JNK） signal pathway in the kidney of rats with diabetic nephropathy. Methods Forty clean, healthy and male Wistar rats were randomly divided into the normal control group（NC group, n =10）, diabetic group（DM group, n =10）, sitagliptin intervention group 1（ST1 group, 5 mg, n=10）, sitagliptin intervention group 2（ST2 group, 10 mg, n=10）. The experiment lasted 16 weeks. The 24 h urinary albumin, urea nitrogen（BUN）, and serum creatinine（Scr） were determined, and the creati-nine clearance rate（Ccr） was caculated. The kidney tissues were determined by paraffin section. HE staining was used to determine the pathological changes of the kidney tissues. Immunohistochemistry and real-time PCR were used to measure the protein and gene expression of Nephrin and JNK-related protein, c-Jun protein, in the kidney. Results Compared with DM group, significantly decreased 24 h urine albumin, and blood BUN and Scr, and relieved patho-logical changes of the kidney tissues were found in ST1 and ST2 groups, and the difference were statistically signifi-cant（P〈0.05）; compared with ST1 group, the changes of the above indicators in ST2 group were more significant.Compared with DM group, increased nephrin protein and gene expression, and decreased c-Jun protein and gene expression were found in ST1 and ST2 groups（P〈0.05）; and the changes in ST1 group were more significant than those in ST2 group. Conclusion Sitagliptin may up-regulate the expression of sertoli cell Nephrin by inhibiting the activity of JNK signal pathway in the kidney of rats with diabetic nephropathy, which produce effective protection for kidney.
出处
《中国药物与临床》
CAS
2016年第3期333-335,共3页
Chinese Remedies & Clinics
基金
山西省青年科技研究基金(2013021035-1)
山西省卫计委科研基金(2014001)
