真武汤对IgA肾病大鼠血液高凝状态的影响

Effects of Zhenwu Decoction on Hypercoagulable State in Rats with IgA Nephropathy

【目的】观察真武汤对IgA肾病大鼠血液高凝状态的影响,探讨真武汤对IgA肾病的治疗作用。【方法】选用雄性SD大鼠60只,随机分为6组,分别为空白对照组,模型对照组,肾炎四味片组(剂量为0.864 g·kg-1·d-1),真武汤高、中、低剂量组(剂量分别为16.8、8.4、4.1 g·kg-1·d-1),每组10只。采用联合应用牛血清白蛋白(BSA)+脂多糖(LPS)+CCl4的方法制备实验性IgA肾病大鼠模型。造模成功后,连续灌胃给药4周。采用血凝仪测定各组大鼠的凝血指标,包括凝血酶原时间(PT)、凝血酶原活动度(PTA)、活化部分凝血酶时间(APTT)、凝血酶时间(TT)以及血浆纤维蛋白原(FIB);采用比浊法测定血小板最大聚集率(PAR)、5 min聚集率(PAR-5)及解聚率(PDR)。【结果】与空白对照组比较,模型组大鼠PT、凝血酶原国际标准化比值(INR)、APTT均显著缩短,而TT、PTA显著延长,FIB含量及PAR、PAR-5均显著上升(P<0.05或P<0.01)。与模型组比较,真武汤高剂量组对大鼠INR、APTT、TT和FIB均有显著影响(P<0.05或P<0.01),但对PT、PTA均无显著影响(P>0.05),而中、低剂量组对大鼠治疗效果均不明显;真武汤各剂量组对二磷酸腺苷(ADP)诱导的血小板聚集有不同程度的抑制作用,尤以高剂量组的抑制作用最为明显,抑制率可达10.67%。【结论】真武汤可改善IgA肾病大鼠的机体高凝状况,同时增强机体血小板的抗聚功能,提高血小板解聚能力,减少凝血功能障碍,延缓肾功能的恶化。

Objective To observe the effect of Zhenwu Decoction on hypercoagulable state in rats with IgA nephropathy, and to explore the therapeutic effecacy of Zhenwu Decoction for IgA nephropathy. Methods Sixty healthy male SD rats were randomly divided into six groups, namely blank control group, model control group, Shenyan Siwei Tablets （ at the dose of 0.864 g-kg-l-d-1） group, high-, middle- and low-dose Zhenwu Decoction groups （at the dose of 16.8, 8.4 and 4.1 g.kg-l.d-1）, 10 rats in each group. The experimental IgA nephropathy rats were induced with bovine serum albumin （BSA） , lipopolysaccharide （LPS） and carbon tetrachloride （CC14） . After modeling, the rats except for the blank control group were given oral administration of the corresponding drugs for 4 weeks. The prothrombin time （PT） , prothrombin activity （PTA）, activated partial thromboplastin time （AP＇IT）, thrombin time （TT） and fiber fibrinogen （FIB） were tested by blood coagulation analyzer. The maximum platelet aggregation rate （PAR）, 5-minute platelet aggregation rate （PAR-5） and platelet depolymerization rate （PDR） were detected by turbidimetric method. Results Compared with the blank control group, PT, prothrombin international normalized ratio （INR） and APTF were significantly shortened, TT and PTA were prolonged, FIB, PAR and PAR-5 were increased （P〈0.05 or P〈0.01） in the model group. Compared with the model group, high-dose Zhenwu Decoction had an effect on improving INR, APTT, TT and FIB obviously （P〈0.05 or P〈0.01）, but had no effect on PT or PTA （P〉0.05）. Middle- and low-dose Zhenwu Decoction had no obvious therapeutic effecacy. Zhenwu Decoction groups showed various degrees of inhibitory effect on platelet aggregation induced by adenosine diphosphate, and high-dose Zhenwu Decoction group had the best effect, whose inhibition rate arrived to 10.67%. Conclusion Zhenwu Decoction can improve the hypercoagulable state in rats with IgA nephropathy, enhance platelet anti-aggregation activity, increase platelet depolymerization capacity and relieve coagulation disorders, showing protective effect on renal function.