复方鱼腥草改善db/db小鼠肾损伤及对JAK/STAT通路部分基因的影响

目的:比较复方鱼腥草不同提取部位对db/db小鼠肾损伤和JAK/STAT通路中部分基因的影响,探讨其防治糖尿病肾病的机制。方法:8周龄的db/m和db/db小鼠分为7组:db/m小鼠为正常组,db/db小鼠分为模型组,JAK酶抑制剂治疗组(AG490,1 mg·kg-1),复方鱼腥草石油醚提取部位组(SYM组),复方鱼腥草乙酸乙酯提取部位组(YSYZ组),复方鱼腥草正丁醇提取部位组(ZDC组),复方鱼腥草水提组(ST组),ig给药8周(7.8 g·kg-1)。检测小鼠尿白蛋白(Alb),24 h尿蛋白定量,血糖,天冬氨酸转氨酶(AST),丙氨酸转氨酶(ALT);粘连蛋白(FN);RT-PCR检测肾组织中的JAK2mRNA,STAT1mRNA,STAT3mRNA,SOCS-1mRNA的变化。结果:与正常组比较,模型组尿Alb,24 h尿蛋白定量,血糖,FN显著升高(P0.05);与模型组比较,尿Alb,24 h尿蛋白定量,FN均有不同程度的改善,且各提取部位组与水提组比较,复方鱼腥草正丁醇提取部位好于其他组,其中尿Alb与FN降低明显(P0.05)。与模型组比较,AG490组,SYM组,YSYZ组,ZDC组肾组织中的STAT1mRNA表达均明显下降(P0.05);ST组,ZDC组的SOCS-1mRNA表达升高(P0.05);但各治疗组的JAK2mRNA,STAT3mRNA表达没有显著差异。结论:复方鱼腥草能降低尿Alb,24 h尿蛋白定量及FN的分泌,且其正丁醇提取部位好于其他提取物组,并能调节JAK-STAT-SOCS-1相关基因表达,改善糖尿病肾损伤。

Effect of Compound Yuxingcao on Renal Injury of db/db Mice and Some Genes of JAK/STAT Pathway

Objective: To compare the effect of different extraction fractions from compound Yuxingcao on the renal injury and some genes in the JAK/STAT pathway in db/db mice, and further investigate its mechanism in preventing and treating diabetic nephropathy. Method: Eight-week-old db/m and db/db mice were divided into seven groups:the db/m mice normal group, the db/db mice model group, the JAK enzyme inhibitor-treated group (AG490,1 mg·kg^-1), the compound Yuxingcao ether extracted fraction (SYM) group, the ethyl acetate extracted fraction (YSYZ) group, the n-butyl alcohol extracted fraction (ZDC) group and the water extracted compound (ST) group, orally administered with drugs for 8 weeks (7.8 g·kg^-1). The changes in urinary albumin (Alb), 24 h urine protein quantitation, blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fibronectin (FN) were measured. The changes in JAK2mRNA, STAT1mRNA, STAT3mRNA and SOCS-1mRNA in nephridial tissues were detected by RT-PCR. Result: Compared with the normal group, the model group showed significant increases in Alb, 24 h urine protein quantitation, blood glucose, FN (P<0.05). Compared with the model group, urinary Alb, 24 h urine protein quantitation and FN had different degrees of relieves. Compared with the ST group, the ZDC group was better than other extracted fraction groups, particularly in urinary Alb and FN (P<0.05). Compared with the model group, the STAT1mRNA expression in AG490, SYM, YSYZ and ZDC groups were significantly lower (P<0.05);the SOCS-1mRNA expression in ZDC and ST groups were higher (P<0.05). However, JAK2mRNA and STAT3mRNA expressions in all treatment groups had no significant difference. Conclusion: Compound Yuxingcao can reduce urinary Alb, 24 h urine protein quantitation and FN excretion. Its n-butyl alcohol extracted fractions show a better effect than other extracted fractions, and can regulate the gene expressions related to JAK/STAT-SOCS1 and relieve the diabetes kidney injury.