解毒祛瘀滋阴方对MRL/lpr狼疮小鼠CD4^+T细胞MeCP2信号通路的影响

Effect of Jiedu Quyu Ziyin Decoction ( 解毒祛瘀滋阴方) on MeCP2 Signaling Pathway of CD4^+ T Cells in MRL/lpr Lupus Mice

目的探讨解毒祛瘀滋阴方治疗系统性红斑狼疮的可能作用机制。方法 30只MRL/lpr狼疮小鼠随机分成中药组、西药组、模型组各10只,10只C57BL/6小鼠作为对照组。中药组予0.5 g/ml浓度的解毒祛瘀滋阴方水煎剂灌胃,西药组予0.5 mg/ml浓度的醋酸泼尼松片混悬液灌胃,模型组和对照组予蒸馏水灌胃,均每次0.01 ml/g,每日1次,连续干预12周。干预结束后观察小鼠皮毛、活动及浅表淋巴结等一般状态,检测小鼠血清白细胞介素4(IL-4)、γ干扰素(IFN-γ)水平变化;HE染色染色观察肾脏病理改变;检测小鼠脾脏CD4^+T细胞甲基结合蛋白2(MeCP2)m RNA和蛋白的表达水平。结果与模型组比较,中药组小鼠肾脏病理损伤明显改善,血清IL-4、IFN-γ浓度水平降低,MeCP2 m RNA和蛋白表达水平明显升高(P<0.05或P<0.01),且中药组MeCP2蛋白及m RNA表达水平升高较西药组明显(P<0.05或P<0.01)。结论解毒祛瘀滋阴方可能是通过激活MeCP2信号通路,进而抑制系统性红斑狼疮的发病。

Objective To explore the potential mechanism of Jiedu Quyu Ziyin Decoction （解毒祛瘀滋阴方, JQZD） in treating systemic lupus erythematosus. Methods Thirty MRL/lpr lupus mice were randomized into Chinese medicine （CM） group, Western medicine （WM） group and the model group, with 10 mice in each group, and the other 10 C57BL/6 mice were set as the control group. CM group was given 0.5 g/ml of JQZD by gavage, WM group was given 0.5 mg/ml of prednisone acetate tablets suspension by gavage, while the model group and the control group were given distilled water orally. All interventions were given 0. 01 ml/g once a day, for 12 weeks. After the intervention, General statuses of fur, activity and superficial lymph nodes of mice were observed. Serum levels of IL-4 and IFN-γ were detected. The pathological changes of kidney were observed with HE staining. The expression levels of MeCP2 mRNA and protein in CD4 ^＋ T cells in mice spleen were detected. Results Compared with those in the model group, the pathological changes of kidney significantly improved, the serum levels of IL-4 and IFN-γ de- creased, and the expressions of MeCP2 mRNA and protein significantly increased in CM group （ P 〈 0. 05 or P 〈 0. 01 ）. The expressions of MeCP2 protein and mRNA in CM group were significantly higher than that in WM group （P 〈 0. 05 or P 〈 0. 01 ）. Conclusion JQZD may inhibit systemic lupus erythematosus through the activation of MeCP2 signaling pathway.