芦丁通过抑制JAK2-STAT3信号通路活性改善MRL/lpr狼疮小鼠的肾损伤

Protective Effect of Rutin on Renal Lesion of MRL/lpr Mice Through Inhibiting JAK2-STAT3 Signaling Pathway

目的研究芦丁对小鼠系统性红斑狼疮肾损伤的保护作用。方法10只正常雌性Balb/c小鼠为正常对照组,50只雌性MRL/lpr小鼠随机分为5组,模型对照组、醋酸泼尼松组(给予醋酸泼尼松0.1 mg·kg^(-1))及芦丁小、中、大剂量组(给予芦丁25,50,100 mg·kg^(-1))。8周龄时开始连续灌胃给药8周。检测尿蛋白浓度、血清Anti-dsDNA IgG和IgM、白细胞介素(IL)-6、干扰素(IFN)-γ、血肌酐(CRE)、血尿素氮(BUN),采用苏木精-伊红(HE)染色法光镜下观察各组小鼠肾脏组织的病理变化。免疫印迹法检测p-JAK2、JAK2、p-STAT3、STAT3的水平。结果与模型对照组比较,芦丁各剂量组尿蛋白含量、血清BUN、CRE浓度、Anti-dsDNA IgG、IgM的含量均显著下降,肾脏病理性损伤减轻,血清中IL-6和IFN-γ的含量显著减少,p-JAK2、p-STAT3水平有所下调,且呈剂量依赖性。结论芦丁对MRL/lpr自发系统性红斑狼疮小鼠肾损伤有一定保护作用,其机制可能与抑制JAK2-STAT3信号通路活化有关。

Objective To investigate the effect of Rutin on renal injury in mice with systemic lupus erythematosus.Methods Ten female healthy Balb/c mice were set as the normal control group(n=10),and 50 female MRL/lpr mice were randomly divided into five groups(n=10):the model control group,prednisone acetate group(0.1 mg·kg^(-1)),Rutin low-dose group(25 mg·kg^(-1)),Rutin medium dose group(50 mg·kg^(-1)),and Rutin high dose group(100 mg·kg^(-1)).Continuous intragastric administration began at eight weeks of mice age for eight weeks.Urine protein concentration,serum anti-dsDNA IgG and IgM,interleukin(IL)-6,interferon IFN-γ,serum creatinine(CRE),and blood urea nitrogen(BUN)were detected.The pathological changes of renal tissues in each group were observed under a light microscope by hematoxylin-eosin(HE)staining,and clinical observation was made in mice.The levels of P-JAK2,JAK2,p-STAT3 and STAT3 were detected by Western blotting.Results Compared with model control group,Rutin dose groups reduced the levels of urine protein content,serum BUN,CRE concentration.anti-dsDNA IgG,anti-dsDNA IgM in each dose group of rutin decreased significantly,and the pathological injury of the kidney was reduced.The contents of IL-6,IFN-γin serum was significantly reduced.The levels of P-JAK2 and P-STAT3 were down-regulated.In addition,the protective effect of Rutin was dose-dependent.Conclusion Rutin has a protective effect on the renal lesion in MRL/lpr mice,and its mechanism may be related to the inhibition of JAK2-STAT3 signaling pathway activation.