低剂量白细胞介素17A对糖尿病肾病大鼠肾功能保护作用的研究

目的 观察并探讨小剂量白细胞介素17A对糖尿病大鼠肾脏的保护作用.方法 雄性SD大鼠45只,随机分3组:正常对照组、DN组及IL-17A组.DN组及IL-17A组均以高脂高糖饮食联合腹腔注射链脲佐菌素建立糖尿病肾病大鼠模型.IL-17A组给予小剂量IL-17A重组蛋白,连续给药12周后,下腔静脉取血,检测糖化血红蛋白、肌酐、尿素氮等;将大鼠放入水平代谢笼中收集各组大鼠24h尿液,测定大鼠24h尿蛋白;实时荧光定量PCR检测肾组织炎症因子表达;Western blot测定IL-17A蛋白表达情况.结果 DN组及IL-17A组尿蛋白、HbA1c、肌酐、尿素氮均显著高于正常对照组(P＜0.05);IL-17A组尿蛋白、肌酐、尿素氮均显著低于DN组(P＜0.05).DN组大鼠在注射IL-17A后促炎因子表达显著减少,抑制性炎症因子表达显著降低.糖尿病肾病模型大鼠IL-17A蛋白显著减少.结论 IL-17A具有改善糖尿病肾病大鼠肾功能作用,并有可能逆转糖尿病肾病,是治疗糖尿病肾病的有效靶点.

The Study of Protective Effect of Interleukin 17 on Renal Function of Diabetic Nephropathy Rats

Objective To observe and investigate the protective effect of low-dose interleukin-17A on rats with diabetic kidney disease.Methods 45 male SD rats were randomly divided into three groups:normal control group,DN group and IL-17A group.DN group and IL-17A group are induced by high calorie and high sugar diet plus intraperitoneal injection of streptozotocin to build the model of diabetic nephropathy.IL-17A group was given a recombinant protein IL-17A.After continuous administration of 12 weeks,Glycated hemoglobin,creatinine,blood urea nitrogen was detected through vena cava blood.And 24h urine of mouse was collected by metabolic cages.The expression of inflammatory cytokines of renal tissue were detected with real-time PCR.IL-17A protein level was analyzed by Western Blot.Results The urinary protein,HbA1c,creatinine,blood urea nitrogen of DN group and IL-17A group were significantly higher than that of the control group(P ＜ 0.05);the urinary protein,creatinine,urea nitrogen of IL-17A group were significantly lower than DN group (P ＜ 0.05).The pro-inflammatory cytokines expression was significantly reduced after injection of IL-17A.Inhibiting inflammatory cytokines was significantly reduced.A significant reduction of IL-17A protein was observed in diabetic nephropathy model of mouse.Conclusion The IL-17A protein can improve renal function of diabetic rats and might further reverse diabetic nephropathy.This highlights an effective target for the treatment of diabetic nephropathy.