加减青蒿鳖甲汤对MRL/lpr小鼠肾组织IL-17、Tim-3表达的影响

Effect of Modified Qinghao Biejia Decoction on the Expression IL-17 and Tim-3 in Renal Tissue for MRL/lpr Mice

目的:探讨加减青蒿鳖甲汤对自发SLE动物模型MRL/lpr小鼠肾组织IL-17、Tim-3的表达以及肾脏病变的影响。方法:24只MRL/lpr小鼠分为3组,每组8只,模型组予生理盐水,中药干预的2组分别予高、低剂量的加减青蒿鳖甲汤水煎剂浓缩液。用药6周后,ELISA法检测小鼠血清ds-DNA抗体浓度;观察小鼠肾脏病理改变;免疫组化法检测肾组织IL-17、Tim-3的表达水平。结果:中药高剂量组组MRL/lpr小鼠血清ds-DNA抗体浓度显著低于模型组(P=0. 001)和中药低剂量组(P=0. 007);中药高剂量组(P=0. 000)和中药低剂量组(P=0. 000)小鼠狼疮肾炎肾组织活动性指数(AI)评分均显著低于模型组;中药高剂量组IL-17表达的肾髓质评分(P=0. 028)及总评分(P=0. 024)较模型组均有显著性差异;小鼠肾组织Tim-3表达水平评分在各组间无显著差异;小鼠肾组织IL-17表达水平总评分与血清ds-DNA抗体浓度呈正相关(r=0. 5859,P=0. 0026)。结论:高剂量的加减青蒿鳖甲汤可能通过抑制IL-17在肾组织的表达而发挥抑制MRL/lpr小鼠肾损害、控制SLE病情进展的作用,但对MRL/lpr小鼠肾组织Tim-3的表达无显著影响。

Objective: To observe the effect of Modified Qinghao Biejia Decoction( QBD) on the expression of IL-17 and Tim-3 in renal tissue for MRL/lpr mice with spontaneous systemic lupus erythematosus. Methods: Twenty-four female MRL/lpr mice aged 8 to 10 weeks were divided into 3 groups: model group,high-dose herbal medicine group,low-dose herbal medicine group. Mice in the model group were given physiological saline,mice in the high-dose herbal medicine group were given concentrated solution of modified QBD( 19.25g. kg-1.d-1),mice in the low-dose herbal medicine group were given concentrated solution of modified QBD( 9.375g. kg-1.d-1). After medication for 6 weeks,serum concentration of ds-DNA antibody in the high-dose herbal medicine group were detected by ELISA;Pathological changes of the kidneys were evaluated;Expression levels of IL-17 and Tim-3 in renal tissue were detected by immunohistochemistry. Results: Serum concentration of ds-DNA antibody in the high-dose herbal medicine group were detected much lower than the model group( P = 0.001) and the low-dose herbal medicine group( P = 0.007). Activity indexes( AI) of the lupus nephritis in the high-dose herbal medicine group( P = 0.000) and the low-dose herbal medicine group( P = 0.000) were lower than in the model group. The high-dose herbal medicine group had lower expression level of IL-17 both in the renal medulla( P = 0.028) and in the whole kidney than the model group( P = 0.024). Expression level of Tim-3 in kidney tissue of all the three groups had no significant difference. Expression level of IL-17 in kidney tissue had positive correlation with serum concentration of ds-DNA antibody( r = 0.5859,P = 0.0026). Conclusion: High dose Qinghao Biejia Decoction may ameliorate the renal damage and inhibit the progression of SLE through depress the expression of IL-17 in kidney tissue of MRL/lpr mice,but may not affect the expression of Tim-3 in kidney tissue of MRL/lpr mice.