柴黄益肾方对嘌呤霉素氨基核苷诱导大鼠慢性肾病的治疗作用

Effects of Chaihuang-Yishen Formula on rats with chronic nephropathy induced by puromycin aminonucleoside

目的:研究柴黄益肾方对嘌呤霉素氨基核苷(puromycin aminonucleoside,PAN)诱导大鼠慢性肾病的治疗作用。方法:60只Wistar大鼠随机分为假手术组、模型组、福辛普利钠阳性对照组(0．833 mg·kg-1)、柴黄益肾方小、中、大剂量组(0．55,1．1和2．2 g·kg-1),每组10只,除假手术组外其余各组动物均经颈静脉插管一次性注射PAN 50 mg·kg-1,制作大鼠肾病综合征伴局灶节段性肾小球硬化模型,假手术组给予生理氯化钠溶液。各给药组于手术次日起连续灌胃给药23周。观察药物对大鼠24 h尿蛋白定量及血清总蛋白、白蛋白、血清胆固醇、三酰甘油、血清尿素氮、血清肌酐等生化学指标的影响,对肾组织进行病理学观察并对损害程度进行评分,采用免疫组化的方法,观察柴黄益肾方对α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)和转化生长因子(transforming growth factor-β1,TGF-β1)蛋白在肾脏组织表达的影响。结果:柴黄益肾方能明显抑制大量尿蛋白排泄,提高血清总蛋白和白蛋白含量,改善脂代谢紊乱,降低血清尿素氮,改善肾脏病理损伤,降低α-SMA和TGF-β1蛋白在肾脏组织表达。结论:柴黄益肾方能减轻由PAN诱导的肾组织损伤,改善肾功能障碍和脂蛋白代谢紊乱,降低α-SMA和TGF-β1蛋白在肾脏组织表达。

Objective： To investigate with chronic nephropathy. Methods：A model the effects of Chaihuang-Yishen Formula （CYF）on rats of Wistar rats＇ chronic nephropathy was set up by jugular vein injection of PAN at a dose of 50 mg·kg^-1 body weight. The 50 rats with chronic nephropathy were randomly assigned to one of five groups： PAN-model alone, PAN-model with high, median and low doses of CYF（0. 55,1.1 or 2.2 g ·kg^-1 ）, or PAN-model with Fosinopri （ FP,0. 833 mg·kg^-1）. Additional 10 rats were used as sham operation control. All model rats were administered with corresponding compounds for 23 weeks next day after the model establishment. The control rats were fed with normal saline alone. Several blood biochemical tests were measured. All rats were sacrificed under anesthesia to collect kidneys tissues for the histopathological examinations. The impact of the CYF on expression of a-smooth muscle actin（α-SMA）and transforming growth factor-β1 （TGF-β1 ）in kidney tissues was analyzed by immunohistochemical technique. Results： The CYF significantly suppressed the protein excretion and the levels of BUN and creatinine, and increased levels of serum total proteins and albumin. The CYF improved the dysfunctional lipid metabolism and reduced the pathological injuries by kidney disorders. Mo- reover, the CYF inhibited the expression of α-SMA and TGF-β1. Conclusion：The CYF functioned well in the management of PAN-induced chronic nephropathy of rats.