白芍总苷对糖尿病大鼠肾组织Toll样受体信号通路调节的研究  

Effect of total glucosides of paeony on TLR signal pathway in the kidney from diabetic rats

作　　者：章超群[1] 武晓旭 吴永贵[1] 徐兴欣[1] 张炜[1] 王坤[1] 

机构地区：[1]安徽医科大学第一附属医院肾内科,安徽合肥230022

出　　处：《中国药理学通报》2014年第3期58-63,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81270813;81374034);教育部高等学校博士学科点专项科研基金(No20093420110003)

摘　　要：目的探讨白芍总苷(TGP)对糖尿病大鼠肾组织Toll样受体(Toll-like receptors,TLR)信号通路的影响。方法建立链脲佐菌素诱导的大鼠糖尿病模型,将大鼠随机分正常组、糖尿病模型组、TGP给药组(50、100、200 mg·kg-1·d-1灌胃)。8周后应用免疫组化,Western blot及实时定量PCR方法检验大鼠肾组织中TLR2/4信号通路相关蛋白的表达。结果 TGP给药组(50、100、200 mg·kg-1·d-1)大鼠尿蛋白排泄率(AER)水平明显低于糖尿病模型组(P<0.05)。免疫组化显示TGP给药组(50、100、200 mg·kg-1·d-1)肾小管-间质TLR2蛋白表达明显低于糖尿病模型组(P<0.01),肾组织TLR4、ED-1也明显低于糖尿病模型组(P<0.05,P<0.01)。Western blot显示糖尿病肾组织TLR信号通路蛋白TLR2、TLR4、MyD88、p-IRAK1、p-IRF3与NF-κB p65表达明显高于正常组(P<0.01);TGP给药(50、100、200mg·kg-1·d-1)肾组织TLR信号通路相关蛋白表达明显低于糖尿病组(P<0.05,P<0.01)。实时定量PCR显示TGP给药(50、100、200 mg·kg-1·d-1)肾组织TLR2、TLR4、MyD88 mRNA明显低于糖尿病组(P<0.05,P<0.01)。结论TGP可减轻糖尿病大鼠早期肾脏损害,其机制可能与抑制糖尿病大鼠肾组织中TLR信号通路有关。Aim To investigate the regulatory effect of total glucosides of paeony(TGP) on Toll-like receptors(TLR) signal pathway in the kidney from diabetic rats. Methods Diabetes was induced by injection of streptozotocin in rats. Rats were randomly divided into three groups: normal group,diabetic model group,diabetic model treated with TGP. TGP 50,100,200 mg·kg- 1were orally administered once a day for 8 wk.TLR2,TLR4,MyD88,p-IRAK1,p-IRF3 and NF-κB p65 were measured with immunohistochemistry,Western blot and quantitative real-time PCR. Results AER was significantly lower in TGP treatment group(50,100,200 mg·kg- 1·d- 1) than in diabetic model group(P < 0. 05). Immunostaining showed that TGP treatment with 50,100 and 200 mg·kg- 1·d- 1could markedly reduce TLR2 expression in the tubulointerstitium,TLR4 and ED-1 expression in the glomeruli and tubulointerstitium. Western blot analysis showed that the markedly increased levels of TLR2,TLR4,MyD88,p-IRAK1,p-IRF3 and NF-κB p65 in the kidneys of diabetic rat were significantly suppressed by TGP treatment(P < 0. 05,P < 0. 01). Quantitative real-time PCR analysis showed that TLR2,TLR4 and MyD88 mRNA were also markedly increased in the kidneys of the control diabetic rat,but were significantly inhibited by TGP(P < 0. 05,P < 0. 01). Conclusions TGP could ameliorate early renal injury,its mechanism may be at least partly correlated with the suppression of increased TLR signal pathway expression in the kidneys from diabetic rat.

关 键 词：糖尿病肾病 白芍总苷 TOLL样受体 信号通路 巨噬细胞 NF-ΚB 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]