狼疮肾炎小鼠肾组织高迁移率族蛋白B1、Toll样受体、水通道蛋白的表达以及三七注射液的干预机制

Expression of high mobility group box protein 1,Toll-like receptor and aquaporin in renal tissues of mice with lupus nephritis and intervention mechanism of Sanqi Injection

目的探讨狼疮肾炎小鼠高迁移率族蛋白B1(HMGB1)、Toll样受体(TLR)、水通道蛋白(AQP)的表达情况,并分析三七注射液干预狼疮肾炎小鼠的可能机制。方法将15只狼疮肾炎小鼠随机分为模型组、三七组、HMGB1抗体组,各5只,分别给予腹腔注射生理盐水、三七注射液、HMG1/HMGB1单克隆抗体;另设置5只正常小鼠为正常对照组,给予腹腔注射生理盐水。给药6周后处死小鼠,检测小鼠肾组织HMGB1、TLR4、TLR7、TLR9、AQP1、AQP2、AQP3蛋白及mRNA的表达。结果与正常对照组比较,模型组HMGB1、TLR4、TLR7、TLR9、AQP1、AQP2、AQP3蛋白及mRNA表达水平均升高(均P<0.05)。与模型组比较,三七组与HMGB1抗体组的HMGB1、TLR4、TLR7、TLR9、AQP1、AQP2、AQP3蛋白和mRNA表达水平均降低(均P<0.05)。结论HMGB1/TLR信号调控AQP表达可能是狼疮肾炎的发生机制之一;三七注射液可能通过干预HMGB1/TLR信号调控AQP表达发挥治疗狼疮肾炎的作用。

Objective To investigate the expression of high mobility group box protein 1(HMGB1),Toll-like receptor(TLR)and aquaporin(AQP)in mice with lupus nephritis,and to analyze the probable intervention mechanism of Sanqi Injection in lupus nephritis mice.Methods Fifteen mice with lupus nephritis were randomly divided into model group(n=5),Sanqi group(n=5)and HMGB1 antibody group(n=5)injected intraperitoneally with normal saline,Sanqi injection,and HMG1/HMGB1 monoclonal antibody,respectively.In addition,five normal mice were selected as normal control group and were intraperitoneally injected with normal saline.The mice were killed after six weeks of administration,the expression of HMGB1,TLR4,TLR7,TLR9,AQP1,AQP2 and AQP3 proteins and mRNAs in renal tissues of the mice were detected.Results Compared with the normal control group,the model group exhibited higher protein and mRNA expression levels of HMGB1,TLR4,TLR7,TLR9,AQP1,AQP2 and AQP3(all P<0.05).Compared with the model group,the Sanqi and HMGB1 antibody groups yielded decreased protein and mRNA expression levels of HMGB1,TLR4,TLR7,TLR9,AQP1,AQP2 and AQP3(all P<0.05).Conclusion The regulation of AQP expression by HMGB1/TLRsignal may be one of the pathogenesis mechanisms of lupus nephritis.Sanqi Injection exerts a therapeutic effect on lupus nephritis probably by interfering HMGB1/TLRsignal to regulate AQP expression.