金雀根对高尿酸血症大鼠肾脏Toll样受体信号通路的影响

Effect of Caragana sinica Root on Renal TLRs Signaling Pathway in A Rat Model of HUA

目的:探讨金雀根对高尿酸血症大鼠模型肾脏Toll样受体(TLRs)信号通路的调控作用。方法:将60只SD大鼠预留10只作为对照组,剩余50只采用灌胃氧嗪酸钾(1.5 g/kg)与腺嘌呤(0.1 g/kg)造模,造模成功后随机分为模型组、别嘌醇组、金雀根高剂量组、金雀根中剂量组、金雀根低剂量组,每组10只。金雀根高剂量组、金雀根中剂量组、金雀根低剂量组分别灌胃金雀根水煎液(5.4 g/kg、2.7 g/kg、1.35 g/kg),别嘌醇组灌胃别嘌醇(50 mg/kg),对照组、模型组分别灌胃生理盐水(10 mL/kg),连续灌胃14 d。治疗结束后采集血清用于肾功能检测;采集肾脏组织样本进行苏木精-伊红(HE)法染色观察;采用蛋白质免疫印迹法(WB)检测肾脏Toll样受体4(TLR4)、Toll样受体4(TLR2)、髓样分化因子88(MyD88)、白细胞介素1β(IL-1β)蛋白表达情况。结果:经金雀根治疗后,大鼠肾脏炎症细胞浸润程度较模型组显著改善;模型组大鼠血清尿酸、尿素氮、肌酐含量均较对照组显著升高(P<0.01),治疗后,别嘌醇组、金雀根高剂量组、金雀根中剂量组、金雀根低剂量组较模型组显著下降(P<0.01);模型组大鼠肾脏组织中TLR2、TLR4、MyD88、IL-1β蛋白表达较对照组显著升高(P<0.05),经药物干预后别嘌醇组、金雀根高剂量组、金雀根中剂量组、金雀根低剂量组蛋白表达较模型组显著下调(P<0.05)。结论:金雀根水煎液可通过下调高尿酸血症大鼠肾脏组织TLRs/MyD88/IL-1β通路关键靶点的表达,抑制组织炎症,进而发挥降尿酸作用。

Objective:To investigate the regulatory effect of Caragana sinica root on the Toll-like receptors(TLRs)signaling pathway in the kidneys of hyperuricemia(HUA)model rats.Methods:Sixty SD rats were used,with 10 reserved to the control group.The remaining 50 rats were given oteracil potassium(1.5 g/kg)and adenine(0.1 g/kg)via gavage to induce HUA.After successful modeling,the rats were randomly divided into a model group,an allopurinol group,and high-dose,medium-dose,and low-dose C.sinica root groups,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups received C.sinica root decoction at doses of 5.4 g/kg,2.7 g/kg,and 1.35 g/kg,respectively.The allopurinol group received allopurinol at 50 mg/kg,while the control and model groups were given saline at 10 mL/kg,all administered via gavage for 14 consecutive days.Serum was collected after treatment for renal function tests,and kidney tissue samples were stained with hematoxylin-eosin(HE)for histopathological examination.Western blot(WB)was used to detect the expression of Toll-like receptor 4(TLR4),Toll-like receptor 2(TLR2),myeloid differentiation factor 88(MyD88),and interleukin-1β(IL-1β)proteins in the kidney tissue.Results:After treatment with C.sinica root,there was a significant reduction in the degree of inflammatory cell infiltration in the kidney tissues compared to the model group.Serum levels of uric acid,blood urea nitrogen,and creatinine were significantly elevated in the model group compared to those in the control group(P<0.01).After treatment,these levels significantly decreased in the allopurinol and high-dose,medium-dose,and low-dose C.sinica root groups compared to the model group(P<0.01).The expression of TLR2,TLR4,MyD88,and IL-1βproteins in the kidney tissue was significantly higher in the model group compared to those in the control group(P<0.05).After drug intervention,the expression levels of these proteins were significantly downregulated in the allopurinol and high-dose,medium-dose,and low-dose C.sinica root groups compared to those in the model group(P<0.05).Conclusion:C.sinica root decoction can inhibit tissue inflammation and reduce uric acid levels by downregulating the expression of key targets in the TLRs/MyD88/IL-1βpathway in the kidney tissues of HUA rats.