青蒿素联合羟基氯喹治疗IgA肾病大鼠的实验研究

Experimental Study on Artemisinin Combined with Hydroxychloroquine in Treating Rats with Ig A Nephropathy

目的探讨青蒿素联合羟基氯喹对IgA肾病大鼠的药理作用。方法采用联合牛血清白蛋白(bovine serum album,BSA)+脂多糖(Lipopolysaccharides,LPS)+四氯化碳(carbon tetrachloride,CCl4)方法建立Ig A肾病大鼠模型,选取尿总蛋白较高大鼠共50只,随机分成5组,即模型对照组、青蒿素与羟基氯喹1∶1组(16.7±16.7)mg·kg^(-1)·d^(-1)、青蒿素联合羟基氯喹1∶3组(8.3±25)mg·kg^(-1)·d^(-1)、血尿胶囊组(0.625 g·kg^(-1)·d^(-1))、地塞米松片组(0.078 mg·kg^(-1)·d^(-1)),每组10只,灌胃给药90 d。另取10只大鼠,不做任何处理,正常饲养作为正常对照组。给药90 d后,观察大鼠的一般情况,检测尿蛋白、血尿、血液生化、肾组织IgA荧光及电镜情况。结果与正常对照组比较,模型对照组尿蛋白、血尿及血清肌酐(GRE)、总蛋白(TP)、甘油三酯(TG)均显著增高(P<0.05,P<0.01),而血清尿素(UREA)明显降低(P<0.01),血清IgA水平显著上升(P<0.01),肾组织IgA荧光强度(++)^(+++),电镜检测肾小球发生明显病变。与模型对照组比较,青蒿素联合羟基氯喹1∶3组蛋白尿、血清IgA水平显著降低(P<0.01),肾组织IgA荧光强度(+)显著降低,肾小球病变明显改善。结论运用BSA+LPS+CCl4方法造模15周可建立IgA肾病动物模型。青蒿素联合羟基氯喹可改善IgA肾病大鼠肾小球滤过膜的屏障功能,可调节Ig A肾病大鼠机体免疫反应,降低血清IgA水平,减少免疫复合物IgA沉积,改善IgA肾病大鼠肾脏病理损伤。

Objective To evaluate the pharmacologic action of artemisinin combined with hydroxychloroquine on rats with IgA nephropathy. Methods IgA nephropathy rat model was induced by the combination of bovine serum album （BSA）, lipopolysaccharides （LPS） and carbon tetrachloride （CC14）. Fifty rats with high urinary total protein were randomized into 5 groups, namely model group, 1：1 combination group（artemisinin 16.7 mg·kg（-1）·d（-1） hydroxyehloroquine 16.7 mg·kg（-1）·d（-1）, 1 ： 3 combination group （artemisinin 8.3 mg·kg（-1）·d（-1）） hydroxychloroquine 25 mg·kg（-1）·d（-1）） , hematuria capsules group （0.625mg·kg（-1）·d（-1）） , dexamethasone group （0.078 mg·kg（-1）·d（-1））, 10 rats in each group. The intragastric administration lasted for 90 days. Ten healthy rats without any medication served as the normal control. After administration, the general health state of rats was evaluated, proteinuria, hematuria, and blood biochemistry were examined, and renal IgA fluorescence and renal pathological histology were examined under electron microscope. Results Compared with those in the normal control group, proteinuria, hematuria, blood creatinine and total protein in the model group were increased significantly （P 〈 0.01）, the level of serum IgA was elevatedstrikingly, fluorescence intensity of IgA in renal tissue was （＋＋） - （＋＋＋）, and glomerulus under electron microscope showed obvious lesions. Compared with those in the model group, proteinuria, hematuria, and serum IgA level in the 1 ： 3 combination group were reduced sharply （P 〈 0.01 ）, fluorescence intensity of IgA in renal tissue （＋） was decreased, and glomerulus lesions were much improved. Conclusion IgA nephropathy model can be established after medication with BSA＋LPS＋CCL for a period of 15 weeks. Artemisinin combined with hydroxychloroquine can improve the barrier function of glomerular filtration membrane, regulate the body immune reaction, reduce the serum IgA level, reduce the deposition of IgA immune complex, and alleviate the renal pathological damage of rats with IgA nephropathy.