摘要
目的 观察水蛭干预肾纤维化大鼠的疗效,并通过TLR4/NF-κB信号通路探讨其对炎症状态的干预机制.方法 将雄性SD大鼠50只,按随机数字表法分为五组:正常组、模型组、阳性对照组和水蛭低、高剂量组.以单侧输尿管梗阻建立肾纤维化模型.干预21天后,生化检测血肌酐、尿素氮,ELISA检测大鼠血清IL-1β、IL-6、TNF-α含量水平,HE、Masson染色光镜下观察大鼠肾脏病理改变,Western blot检测肾组织内TLR4、MyD88、NF-κB蛋白表达.结果 与正常组比较,模型组血Scr、BUN显著升高(P＜0.01),血IL-1β、IL-6、TNF-α水平均显著升高(P＜0.01),大鼠肾脏组织发生明显病理改变,大鼠肾脏组织中TLR4、MyD88、NF-κB蛋白表达均显著升高(P＜0.01);与模型组比较,阳性对照组、水蛭低、高剂量组血清Scr、BUN、IL-1β、IL-6、TNF-α水平均显著降低(P＜0.01),肾脏组织病理显著改善,肾脏组织中TLR4、MyD88、NF-κB蛋白水平均明显降低(P＜0.05).结论 水蛭能有效改善肾纤维化大鼠的肾功能,其机制可能是抑制TLR4/NF-κB信号通路从而抑制炎症反应发生,达到抗肾纤维化的目的.
Abstract
Objective To observe the therapeutic effect of hirudo on renal fibrosis in rats,and to explore the mechanism of TLR4/NF-κB signal pathway on inflammatory state.Methods Fifty male SD rats were randomly divided into five groups:control group,RIA model group,positive control group and leech low and high dose groups.The model of tubulointerstitial fibrosis was established by unilateral ureteral obstruction.After 21 days of intervention,serum creatinine and urea nitrogen were detected by biochemistry,and serum IL-1 β,IL-6,TNF-αwas detected by ELISA;The pathological changes of rat kidneys were observed by HE and Masson staining under light microscope,and TLR4,MyD88 and NF-κB protein expression in renal tissues were de-tected by Western blot.Results Compared with the control group,the blood Scr and BUN in the model group were significantly in-creased(P＜0.01),The levels of IL-1β,IL-6,TNF-αwere significantly increased(P＜0.01),The kidney tissue of the rats had obvious pathological changes,the expression ofTLR4,MyD88,NF-κB protein in rat kidney increased significantly(P＜0.01);Compared with the RIA model group,the positive control group and leech low and high dose groups had the levels of serum Scr,BUN,IL-1 β,IL-6,TNF-αsignificantly decreased(P＜0.01);The renal histopathology was improved significantly,The levels of TLR4,MyD88,NF-κB in renal tissue were significantly decreased(P＜0.05).Conclusion Leech can effectively im-prove the renal function of rats with renal fibrosis,and its mechanism may be to inhibit TLR4/NF-κB signal pathway can inhibit the occurrence of inflammatory reaction and achieve the purpose of anti renal fibrosis.
基金项目
广西自然科学基金(2020GXNSFAA259086)
国家自然科学基金(82060804)
广西中医药大学科学研究课题(2020MS022)
广西中医药大学科学研究课题(2022MS010)
广西名中医史伟传承工作室项目(院医字[2017]11号)
广西自然科学基金面上项目(2020GXNSFAA297200)
桂派杏林拔尖人才项目(桂中医大202223)
NETL
NSTL
万方数据