四逆汤及其不同配伍方对心力衰竭大鼠的保护作用及机制探讨

Effect and Mechanism on Doxorubicin-induced Heart Failure of Sini Tang and Its Components Compatibility in Rats

摘要:

目的: 研究四逆汤及其不同配伍方对阿霉素诱导大鼠心力衰竭的保护作用及可能的作用机制。方法: SPF级雄性SD大鼠85只,其中75只大鼠采用ip阿霉素(2.5 mg·kg^-1)法,每周1次,共6周,建立大鼠慢性心力衰竭模型。将造模成功大鼠随机分为模型组,附子组(1.5 g·kg^-1),附子-甘草组(3 g·kg^-1),附子-干姜组(2.5 g·kg^-1),四逆汤组(4 g·kg^-1)及卡托普利阳性药组(6.25 mg·kg^-1),并另设正常组10只。各治疗组连续ig给药4周,模型组和正常组予同体积蒸馏水。末次给药后,称取各组全心和左心室质量,计算心重指数;取左心最大横切部位HE病理染色,观察心肌组织形态学变化;ELISA法检测血液中大鼠脑钠肽(BNP)、大鼠血管紧张素Ⅱ(AngⅡ)和大鼠醛固酮(ALD)水平。结果: 与正常组比较,心衰模型组大鼠左心室质量指数(LVWI)和全心质量指数(HWI)明显增加(P<0.05),大鼠血清BNP,AngⅡ和ALD含量较正常组显著升高(P<0.01),组织形态学观察发现正常组心肌细胞排列整齐,细胞大小均一,模型组出现心肌纤维排列紊乱,胞质疏松,细胞肿胀等现象。与模型组比较给予四逆汤干预后,各用药组大鼠心肌病变情况均较模型组有不同程度改善,以四逆汤组改善情况显著,HWI指数明显减低(P<0.05),各治疗组较模型组大鼠血清BNP,AngⅡ和ALD含量及LVWI指数均有不同程度的下降(P<0.05),且四逆汤组在降低BNP和ALD水平上优于附子组(P<0.05)。结论: 四逆汤及其不同配伍方通过减轻心衰大鼠的症状,减缓心脏重塑,抑制神经内分泌因子的过度激活,多靶点、多途径的预防和缓解CHF的发生和发展,以四逆汤全方抗心衰效应更为明显,附子配干姜能部分改善相应指标,附子配甘草的强心作用较弱,单用附子的作用最弱。

Abstract:

Objective: To study the protective effect and mechanisms of Sini Tang (SNT) and its components compatibility on chronic heart failure (CHF) induced by doxorubicin in rats. Method: The CHF rat model was induced by intraperitoneal injection of doxorubicin (ADR, 2.5 mg·kg^-1) once a week for 6 weeks. The successful model rats were randomly divided into 6 groups:the model group, the Aconiti Lateralis Radix Praeparata group (ALRP, 1.5 g·kg^-1), the ALRP-Glycyrrhizae Radix et Rhizoma group (ALRP-GRR, 3 g·kg^-1), the ALRP-Zingiberis Rhizoma group (ALRP-ZR, 2.5 g·kg^-1), the SNT group (4 g·kg^-1) and the captopril group (6.25 mg·kg^-1). Meanwhile, another 10 normal rats were assigned to the normal group. The rats in the treatment groups receive the corresponding medicines by intragastric administration for 4 weeks and the rats in the normal and the model group received the same volume of distilled water. After the last administration, left ventricular weight index (LVWI) and heart weight index (HWI) were measured. The pathological changes in myocardial muscle of rats were observed using HE staining. B-type natriretic peptide (BNP), angiotensin Ⅱ (angⅡ) and aldosterone (ALD) were assayed by ELISA. Result: Compared with the normal group, the LVWI and HWI increased obviously (P<0.05), the BNP, AngⅡ and ALD levels were significantly higher (P<0.01) in the model group. Compared with the model group, HWI was reduced in the SNT group (P<0.05), the BNP, AngⅡ and ALD level were lower in all treatment groups (P<0.05). Furthermore, the results of SNT were better than ALRP in reducing the level of BNP and ALD in serum. Conclusion: SNT and its components compatibility have protective effect on CHF induced by ADR in rats. The mechanism may be related to attenuating cardiac remodeling and inhibiting the excessive activation of neuroendocrine factor. SNT has obvious effect of anti-heart failure. ALRP-ZR group could partly improve the cardiac function of CHF. ALRP-GRR group has superior cardiotonic effect to the application of ALRP alone.