小檗碱抗实验性心肌肥厚的作用及机理研究

【作者】 赵海苹；

【导师】 洪缨；

【作者基本信息】 北京中医药大学 ， 中西医结合基础， 2006， 硕士

【摘要】 心肌肥厚是心肌工作超负荷的一种适应性反应,以心肌细胞蛋白合成增加和细胞体积增大为主要特征,还有心肌间质成分和血管结构的变化,长期的负荷应激会导致不良的心肌重构,心肌收缩力减弱,增加了心律失常的危险性并最终导致心力衰竭,一些主要心脏病的发病率和死亡率可因左心室肥厚的存在明显增加。现有一些学者认为,心室肥厚即使在早期也是一种有害的反应。因此,抑制心室肥厚的发生和发展是防治心衰的一项重要措施。小檗碱(berberine)是黄连、黄柏等清热类中药中所含的主要生物碱,以往的研究显示其具有广泛心血管药理活性,如降压、抗心律失常等。本课题着重研究小檗碱对双肾双夹及甲状腺素模型心肌肥厚的干预作用,并对相关机制如血流动力学、神经体液因素以及能量代谢进行了初步探讨。1小檗碱对心肌肥厚动物模型心肌重构的影响1.1小檗碱对双肾双夹模型大鼠心肌重构的影响方法:采用双肾双夹的方法制备心肌肥厚模型,造模2周开始给小檗碱,以卡托普利为阳性对照药,连续给药4周后处死动物,摘取心脏,计算全心重量指数(HW/BW)、左心室重量指数(LVW/BW)及右心室重量指数(RW/BW),以心重(g)/体重(kg)表示。测定左心室肌组织胶原含量。取左心室赤道面心肌环作石蜡切片,进行HE染色,在普通显微镜下观察左心室形态,测量左心室壁厚度(LVWT)、室间隔厚度(IVST);进行天狼星红染色,在偏光显微镜下用Image-ProPlus5.0图像分析软件测定心肌间质胶原容积分数(ICVF)及血管周围胶原面积(PVCA)。结果:小檗碱10mg/kg可显著降低双肾双夹心肌肥厚模型的HW/BW(P<0.05)、LVW/BW(P<0.05)、RW/BW(P<0.05)。降低LVWT(P<0.05)。降低ICVF(P<0.01)及PVCA(P<0.05)。1.2小檗碱对甲状腺素模型大鼠心肌重构的影响方法:皮下注射甲状腺素制备心肌肥厚模型,造模2周开始给小檗碱,以美托洛尔为阳性对照药,连续给药2周后处死动物,摘取心脏,计算全心重量指数(HW/BW)、左心室重量指数(LVW/BW)及右心室重量指数(RW/BW),以心重(g)/体重(kg)表示。测定左心室肌组织胶原含量。结果:小檗碱各组可显著降低甲状腺素心肌肥厚模型的HW/BW(P<0.05)、LVW/BW(P<0.05)。小檗碱5mg/kg可显著降低模型大鼠左心室肌组织胶原含量。结论:小檗碱对结扎双侧肾动脉以及注射甲状腺素引起的心肌肥厚有一定的抑制作用,并能减轻心肌间质及血管周围胶原增生。2小檗碱对心肌肥厚动物模型血流动力学的影响更多还原

【Abstract】 Cardiac hypertrophy, especially left ventricular hypertrophy (LVH) is a common pathway of the final stage of many cardiopathies, which has become an major risk factor, and a powerful independent predictor for the cardiovascular events. Although LVH in hypertension can be considered an adaptive response to reduce wall stress, LVH precedes the development of chronic heart failure. The regression of structural remodelling in hypertensive heart disease represents a goal of pharmacological intervention as a reduction in blood pressure in arterial hypertension may be unable to reduce fibroblast growth and collagen turnover. Therapeutic strategies have included the use of angiotensin-converting enzyme (ACE)-inhibitors, angiotensin II type 1 receptor antagonists, antagonists of aldosterone receptors, Calcium Channel Blockers (CCB) and antagonists of endothelin A and B receptors. But there are also some antihypertensive drugs such as Minoxidil which would aggravate myocardial ischemia and/or left ventricular hypertrophy as well as decrease the blood pressure.Berberine is the primary effective compound of a Chinese herb, Coptis chinensis Franch (coptis), it has been widely applied in treating some cardiovascular diseases, such as hypertension and chronic heart failure. Ber’s cardiovascular effect include antihypertension, positive inotropic, negative frequency, antiarrhythmia, and also could protect from heart failure and damnification after ischaemic-reperfusion. The aim of the present study, therefore, was to evaluate the effect of berberine on the development of detrimental chamber and interstitial remodeling in two-kiney two-clip rat model and L-thy-induced cardiac hypertrophy rat model, and intended to explain some underlined mechanism of its action.1 Berberine’effect on left ventricular remodeling in cardiac hypertrophy model rats1.1 Berberine’s effect on left ventricular remodeling in 2K2C model ratsMethod: The cardiac hypertrophy model was established by the operation of two-kidney two-clip, two weeks later, berberine was given by gastrogavage for 4 weeks, then executed the rats, took the hearts out, calculated the HW/BW, LVW/BW, RW/BW. Measured the content of Hyp in the left ventricule. Took the equator annulus of left ventricular as paraffin slice, processed HE and Sirius red staining seperately, left ventricular wall thickness (LVWT), interventricular septal thickness (IVST), interstitial collagen volume fraction (ICVF) and perivascular collagen area (PVCA)更多还原