降糖益肾丸对糖尿病肾病大鼠肾Toll样受体4和炎症因子的影响

Effect of Jiangtang Yishen Pills on Renal Toll-Like Receptor 4and Inflammatory Factors in Diabetic Nephropathy Rats

目的:探讨降糖益肾丸治疗糖尿病肾病(DN)的作用机制。方法:36只SPF级雄性SD大鼠随机分为6组:空白对照组、DN模型组、DN模型+降糖益肾丸组(高剂量组)、DN模型+降糖益肾丸组(中剂量组)、DN模型+降糖益肾丸组(低剂量组)、DN模型+盐酸二甲双胍+厄贝沙坦组(阳性药组),每组6只。空白对照组给予普通饲料喂养,其余各组大鼠采用高脂高糖饮食联合链脲佐菌素(STZ)注射造模,药物组给药28天后,分别测定各组大鼠血清炎性因子白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的含量,酶联免疫(ELISA)分析肾组织中TLR4、NF-κB p65蛋白表达水平的变化。结果:与对照组比较,模型组大鼠IL-6、TNF-α、TLR4和NF-κB p65表达均显著升高(P<0.01)。与模型组比较,阳性药组与中、高剂量组大鼠IL-6、TNF-α、TLR4和NF-κB p65表达均显著下降,低剂量组大鼠IL-6、TNF-α、TLR4和NF-κB p65表达亦下降(P<0.01或P<0.05)。与中、高剂量组比较,低剂量组IL-6、TNF-α、TLR4和NF-κB p65表达显著升高(P<0.01)。结论:降糖益肾丸能显著降低DN大鼠的肾炎症水平,该作用可能与其下调TLR4和NF-κB p65表达相关。

Objective:To explore the mechanism of Jiangtang Yishen Pills in treating diabetic nephropathy rats.Methods:36SD rats were randomly divided into 6groups:blank control group,model group,DN model+Jiangtang Yishen pills group(high dose group),DN model+Jiangtang Yishen pills group(middle dose group),DN model+Jiangtang Yishen pills group(low dose group),DN model+metformin hydrochloride+irbesartan group(positive drug group),6rats in each group.The rats in the blank control group were fed with normal diet,and the rats in the other groups were fed with high-fat and high-sugar diet combined with streptozotocin(STZ)injection for modeling.After 28days of administration in the drug group,the contents of serum inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in each group were determined,and the changes of TLR4and NF-κB p65protein expression levels in renal tissue were analyzed by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the control group,the expressions of IL-6,TNF-α,TLR4and NF-κB p65in the model group were significantly increased(P<0.01).Compared with the model group,the expressions of IL-6,TNF-α,TLR4and NF-κB p65in the positive drug group,middle and high dose groups were significantly decreased,and the expressions of IL-6,TNF-α,TLR4and NF-κB p65in the low dose group were also decreased(P<0.01or P<0.05).Compared with medium and high dose groups,the expressions of IL-6,TNF-α,TLR4and NF-κB p65in low dose group were significantly increased(P<0.01).Conclusion:Jiangtang Yishen Pills can significantly reduce the level of renal inflammation in DN rats,which may be related to down-regulating the expression of TLR4and NF-κB p65.