氯沙坦钾对糖尿病大鼠肾脏内质网应激及炎症反应的作用研究

Effect of losartan potassium on endoplasmic reticulum stress and inflammatory response in the kidney of diabetic rats

目的探讨氯沙坦钾在糖尿病大鼠肾脏内质网应激以及炎症反应中的作用。方法选取30只SD雄性大鼠,以随机分组的方式将其分为对照组(10只)、模型组(10只)和氯沙坦钾组(10只)。模型组和氯沙坦钾组大鼠进行腹腔注射链脲佐菌素以建立糖尿病大鼠模型,对照组注射相同体积的枸橼酸钠缓冲液。模型建立后,氯沙坦钾组给予每日氯沙坦钾灌胃,持续4周。使用逆转录-聚合酶链反应检测肾组织中c-Jun氨基末端激酶(JNK)、C/EBP同源蛋白(CHOP)、人巨噬细胞趋化蛋白-1(MCP-1)的mRNA表达,使用蛋白质印迹法检测大鼠肾组织中JNK、p-JNK、CHOP、MCP-1蛋白的表达情况。结果4周后,模型组与氯沙坦钾组的24 h尿蛋白定量均高于对照组,且氯沙坦钾组低于模型组(P<0.05);三组的肾组织中JNK mRNA水平差异无统计学意义(P>0.05),模型组与氯沙坦钾组的CHOP、MCP-1 mRNA表达水平均高于对照组,且氯沙坦钾组低于模型组(P<0.05);三组JNK蛋白的表达水平差异无统计学意义(P>0.05);氯沙坦钾组与模型组的p-JNK、CHOP、MCP-1蛋白的表达水平均高于对照组,且氯沙坦钾组低于模型组(P<0.05)。结论氯沙坦钾可以降低JNK/CHOP通路蛋白的表达,从而抑制内质网应激,同时减少炎症反应,达到保护肾脏的作用。

Objective To discuss the effect of losartan potassium on endoplasmic reticulum stress and inflammatory response in the kidney of diabetic rats.Methods Thirty SD male rats were selected,and randomly assigned into three groups,each with 10 rats.Rats in model group and losartan potassium group were given intraperitoneal injections of streptozotocin to establish a diabetic rat model,and rats in the control group were injected with an equal volume of sodium citrate buffer solution.After model establishment,losartan was given daily by gavage to losartan potassium group for 4 weeks.The mRNA and protein expression levels of c-Jun N-terminal kinase(JNK),C/EBP homologous protein(CHOP),and monocyte chemotactic protein-1(MCP-1)in kidney tissues were detected using reverse transcription polymerase chain reaction,and the protein expression levels of JNK,phosphorylated c-Jun N-terminal kinase(p-JNK),CHOP and MCP-1 were measured by western blotting.Results After 4 weeks,the 24 h urine protein quantification values among three groups were the smallest in control group,followed by losartan potassium group,and were the largest in model group,with statistical difference(P<0.05).The mRNA expression of JNK in the kidney tissues yielded no statistical difference among three groups,while the mRNA expression of CHOP and MCP-1 were the lowest in control group,followed by losartan potassium group,and were the highest in model group,with statistical difference(P<0.05).No statistical difference was found in the protein expression levels of JNK,while the protein expression levels of p-JNK,CHOP and MCP-1 were the lowest in the control group,followed by losartan potassium group,and were the highest in model group,with statistical difference(P<0.05).Conclusion The renoprotective effects of losartan potassium may be associated with down-regulated expression of JNK/CHOP pathway related proteins,inhibition of endoplasmic reticulum stress,and attenuation of the inflammatory response.