雷公藤甲素减轻MRL/lpr狼疮小鼠肾损伤的作用机制研究

Effect and mechanism of Triptolide on ameliorating renal injury of MRL/lpr lupus mice

目的研究雷公藤甲素(TPL)减轻MRL/lpr狼疮小鼠肾损伤的作用及其机制。方法选择雌性C57BL/6正常小鼠作为对照组;将雌性MRL/lpr狼疮小鼠分为模型组、TPL组、JAK1组、TPL+JAK1组。给药9周后检测各组24 h尿蛋白、血清肌酐(Scr)、血尿素氮(BUN)水平及血清IP-10、高迁移率族蛋白1(HMGB1)的质量分数,肾脏IgG、C3的荧光强度、γ干扰素诱导蛋白10(IP-10)、HMGB1的质量分数、磷酸化Janus激酶1(p-JAK1)、磷酸化信号传导及转录激活蛋白1(p-STAT1)的表达水平。结果模型组小鼠24 h尿蛋白、Scr、BUN及IgG、C3的免疫荧光强度、IP-10、HMGB1、p-JAK1、p-STAT1均高于对照组(P<0.05);TPL组小鼠24 h尿蛋白、Scr、BUN及IgG、C3荧光强度、IP-10、HMGB1、p-JAK1、p-STAT1均低于模型组(P<0.05);TPL+JAK1组小鼠24 h尿蛋白、Scr、BUN及IgG、C3荧光强度、IP-10、HMGB1、p-JAK1、p-STAT1均高于TPL组(P<0.05)。结论TPL减轻MRL/lpr狼疮小鼠肾损伤的分子机制可能是抑制JAK1/STAT1通路介导的炎症反应。

Objective To study the effect and mechanism of triptolide(TPL)on ameliorating renal injury of MRL/lpr lupus mice.Method Female C57BL/6 normal mice were selected as the control group,female MRL/lpr lupus mice were divided into model group,TPL group,JAK1 group and TPL+JAK1 group.24h urine protein,serum creatinine(Scr),blood urea(BUN),fluorescence intensity of renal IgG and C3,contents of IFN-γinduced protein 10(IP-10)and high mobility group box protein 1(HMGB1),the expression of phosphorylated Janus kinase 1(p-JAK1),phosphorylated signal transduction and activator of transcription 1(p-STAT1)were detected.Result The 24 h urine protein,Scr,BUN levels,IgG and C3 fluorescence intensity,IP-10 and HMGB1 content,p-JAK1 and p-STAT1 expression in model group were higher than those in control group(P<0.05);the 24 h urine protein,Scr,BUN levels,IgG and C3 fluorescence intensity,IP-10 and HMGB1 content,p-JAK1 and p-STAT1 expression in TPL group were lower than model group(P<0.05);the 24 h urine protein,Scr,BUN levels,IgG and C3 fluorescence intensity,IP-10 and HMGB1 content,p-JAK1 and p-STAT1 expression in TPL+JAK1 group were higher than those in TPL group(P<0.05).Conclusion TPL can ameliorate renal damage in MRL/lpr lupus mice,and the inhibitionof inflammatory response mediated by JAK1/STAT1 pathway is a possible molecular mechanism.