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目的:探讨雷至胶囊(雷公藤多苷10 mg.kg-1+女贞子、墨旱莲4 g.kg-1)在治疗嘌呤霉素氨基核苷(PAN)肾病的减毒增效作用。方法:80只雄性大鼠随机分为8组:空白组、模型组、雷至胶囊高、低剂量组、雷公藤多苷高、低剂量组、雷公藤甲素组和缬沙坦组,每组10只。颈静脉注射PAN 100 mg.kg-1建立PAN肾病模型。空白组颈静脉注射等量生理盐水。其余各治疗组造模后第2天开始每日分别ig给药,持续10 d。第11天,处死大鼠,摘取肝肾,用于光镜、免疫荧光及透射电镜检测。结果:一般情况:模型鼠第5天尿量减少、腹水,而浮肿不明显,体重下降。第7～10天腹水明显,24 h尿蛋白增加,死亡率30%(3/10)。病理改变:模型鼠肾小管上皮细胞变性,电镜下,可见足细胞足突融合、消失,而空白组足细胞结构正常。各药物治疗组24 h尿蛋白、血生化、血红蛋白均有不同程度改善,各治疗组血尿素氮轻度升高(P<0.05)。雷至胶囊及雷公藤多苷10 mg.kg-1组降蛋白尿、改善贫血、降低AST疗效优于其余各组,电镜下,雷至胶囊高剂量组足突融合减轻,足突明显恢复。结论:雷至胶囊可能通过降低PAN肾病大鼠蛋白尿、改善贫血、降低AST、减轻足细胞足突融合及肾小管上皮细胞变性等发挥减毒增效作用。
Objective: To investigate the attenuating and synergistic effects of Leizhi Capsule (TGP) 10 mg.kg-1 + Ligustrum lucidum and 4 mg.kg-1 of Eclipta Herb on puromycin aminonucleoside (PAN) nephropathy . Methods: 80 male rats were randomly divided into 8 groups: blank group, model group, Leizhi Capsule high- and low-dose group, Tripterygium glycosides high- and low-dose group, triptolide group, and valsartan group. Group 10 only. A PAN nephropathy model was established by jugular vein injection of PAN 100 mg.kg-1. The blank group was intravenously injected with equal volume of saline. The rest of the treatment groups were given daily ig administration twice daily for the first 10 days after modeling. On the eleventh day, the rats were sacrificed and the liver and kidneys were removed for light microscopy, immunofluorescence and transmission electron microscopy. RESULTS: In general, the urine volume and ascites decreased on the 5th day in the model rats, but the edema was not obvious and the body weight decreased. On the 7th to the 10th day, the ascites was obvious, and the 24-hour urine protein was increased, and the mortality rate was 30% (3/10). Pathological changes: renal tubular epithelial cells in model rats were degenerated. Electron microscopy showed that the podocyte foot processes merged and disappeared, while in the blank group, the podocyte structure was normal. 24 h urinary protein, blood biochemistry and hemoglobin were improved to varying degrees in each drug treatment group, and blood urea nitrogen was slightly elevated in each treatment group (P<0.05). Leizhi capsule and Tripterygium glycosides 10 mg.kg-1 group had better effect of reducing proteinuria, improving anemia, and reducing AST than other groups. Under electron microscope, foot fusion of Leizhi capsule high-dose group decreased, and foot processes remarkably recovered. Conclusion: Leizhi Capsule may play a role in attenuating and synergizing by reducing proteinuria, improving anemia, decreasing AST, reducing podocyte foot process fusion and denuding of renal tubular epithelial cells in rats with PAN nephropathy.