目的观察补肾通络方对阳离子化牛血清白蛋白(C-BSA)致膜性肾炎模型大鼠高凝状态的影响,并探究其作用机制。方法72只雄性SD大鼠随机分为对照组、模型组、泼尼松+阿司匹林给药组和高、中、低剂量补肾通络方给药组。用C-BSA免疫法制备膜性肾炎大鼠模型,给药4周后测定24h尿白蛋白、血小板聚集率、血浆纤维蛋白原(Fib)、肾皮质血栓素B₂(TXB₂)和6-酮-前列腺素F1α(6-keto-PGF_1α)的量。结果模型组大鼠24h尿白蛋白排泄量、血小板聚集率、血浆Fib和肾皮质TXB₂的量均显著高于对照组;补肾通络方给药组的这些检测指标均显著低于模型组;造模后大鼠肾皮质6-keto-PGF_1α量明显减低,补肾通络方给药使其量有所增加。结论补肾通络方能使膜性肾炎大鼠的血小板聚集性、血浆Fib水平和肾皮质TXA₂的量降低,从而改善血液高凝状态和防止肾小球内微血栓形成,这可能是其有效治疗慢性肾炎的重要机制。

Objective This study was designed to assess whether Bushen Tongluo Fang(BSTLF),a Chinese materia medica formula,can ameliorate the hypercoagulable state in rats with membranous glomerulonephritis(MGN)induced by cationized bovine serum albumin(C-BSA)in order to gain an insight into the mechanisms responsible for its therapeutic effect.Methods Seventy-two male Sprague-Dawley rats were randomly separated into six groups:the normal control group,the MGN model group,the prednisone-plus-aspirin treatment group,and the low-,moderate-,and high-dose groups of BSTLF.The model of MGN was induced by sc(preimmunization)and iv injections of C-BSA in the latter five groups.After the development of MGN model,the decoctions of BSTLF and the prednisone-plus-aspirin solution were ig administered to the treatment groups respectively twice daily for four weeks.The rats in the model group received their drinking water as vehicle controls.Urinary albumin excretion for 24 h was measured using a rat albumin ELISA kit.The platelet aggregation was analyzed by turbidimetry.The plasma level of fibri-nogen(Fib)was determined by the von Clauss assay.Radioimmunoassay was used to examine thromboxane B₂(TXB₂)and 6-keto-prostaglandin F_1α(6-keto-PGF_1α)of the renal cortex.Results Urinary albumin excretion for 24 h,maximal platelet aggregation,plasma Fib level,and TXB₂ production of renal cortex in the MGN model group were significantly higher than those in the normal control group,respectively.Compared with the MGN model group,these four measurements were decreased significantly in BSTLF-treated groups.The 6-keto-PGF_1α production of renal cortex in the MGN model group was subnormal but no statistically significant differences were observed between the model group and BSTLF groups.Conclusion The results of this study suggest that the administration of BSTLF could attenuate platelet aggregability,lower plasma level of Fib and reduce thromboxane A2 production by renal cortex in the rats with MGN,so that their hypercoagulable state is corrected at least partly and glomerular microthroimbosis is prevented in several ways.These effects may contribute considerably to the mechanisms of BSTLF efficacy for chronic nephritis.

湖南省科技厅计划项目(05SK3039);湖南省教育厅科研项目(08W011)