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

摘要:

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/TAT1通路介导的炎症反应。

Abstract:

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-γ induced 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 inhibition of inflammatory response mediated by JAK1/STAT1 pathway is a possible molecular mechanism.