目的 探讨苦参碱抗压力超负荷大鼠心室重构的作用及其作用机制。方法 用腹主动脉缩窄方法 复制大鼠压力超负荷心室重构模型。设假手术组,模型组,苦参碱大、中、小剂量(63、31.5、15.75mg/kg)组及阳性药(美托洛尔36mg/kg、卡托普利13.5mg/kg)组。给药3.5个月后测量心率(HR)、动脉收缩压(SBP)、动脉舒张压(DBP)、平均动脉压(MAP)、左心室内压(LVSP)、左室舒张末期压(LVEDP)、左室内压上升下降最大速率(±dp/dtmax;计算左心室质量/体重(LVW/BW)、右心室质量/体重(RVW/BW)、全心室质量/体重(HW/BW);用放射免疫方法 测定左心室心肌肾素活性(RA)及血管紧张素Ⅱ(AngⅡ)的量;用免疫组织化学方法 测定左心室心肌和型胶原蛋白的量;用逆转录-聚合酶链反应法(RT-PCR)测定左心室心肌心房利钠肽(ANP)mRNA、转化生长因子-β1(TGF-β1)mRNA的表达。结果 苦参碱能显著降低压力超负荷致心室重构大鼠的LVW/BW、HW/BW,改善血流动力学参数,降低左心室心肌RA及AngⅡ的量,降低左心室心肌Ⅰ和Ⅲ型胶原蛋白的表达,降低左心室心肌ANP mRNA、TGF-β1 mRNA的表达。结论 苦参碱具有抑制实验性心室重构的作用,其机制与抑制心肌肾素-血管紧张素-醛固酮系统(RAAS)激活,降低左心室心肌ANP mRNA及TGF-β1 mRNA的表达有关。

Objective? To investigate the effect and mechanisms of matrine on ventricular remodeling in press-overload rats in vivo. Methods? The press-overload ventricular remodeling was induced by abdominal aortic banding in rats. Ventricular remodeling model rats were randomly divided into the following groups: Sham group, press-overload model group, Metoprolol group (36 mg/kg), Captopril group (13.5 mg/kg) and matrine groups with various dosages 63, 31.5, and 15.75 mg/kg). After administration of the tested drugs for 3.5 months, HR, SBP, DBP, MAP, LVSP, LVEDP, and ±dp/dtmax were recorded. The left ventricular renin activity (RA) and the content of Ang Ⅱ were measured using radioimmunity assay. The content of type Ⅰ and Ⅲ collagen in left ventricle were determined using immunohistochemical analysis. The ratios of LVW/BW, RVW/BW, and HW/BW were calculated. The mRNA expression levels of ANP and TGF-β1 in left ventricle were determined by RT-PCR. Results? The experimental data demonstrated that matrine could significantly decrease the ratios of LVW/BW and HW/BW, reduce RA and the Ang Ⅱ content in left ventricular muscle, decrease the protein expression of type Ⅰ and Ⅲ collagen, lessen the mRNA expression levels of ANP and TGF-β1 in left ventricle. Conclusion??Matrine could significantly attenuate the experimental ventricular remodeling. The mechanism is related with its ability to inhibit the activation of renin-angiontensin-aldosterone system (RAAS) and also associated with the reduction of the mRNA expression levels of ANP and TGF-β1 in the left ventricle.

国家自然科学基金资助项目(30572379);国家中医药管理局基金资助项目(04DSZP30)