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作 者:周四桂[1] 黄河清[1] 陈少锐[1] 饶曼人[2] 刘培庆[1]
机构地区:[1]中山大学药学院药理与毒理学实验室,广东广州510089 [2]南京医科大学心血管药理研究室,江苏南京210029
出 处:《中国药理学通报》2006年第5期543-547,共5页Chinese Pharmacological Bulletin
基 金:国家自然科学基金资助项目(No39570819);广东省重点攻关资助项目(No2002C30113);珠海市科技局重点资助项目(No2005-4205088)
摘 要:目的研究前胡丙素长期灌胃给药对两肾两夹肾性高血压大鼠心脏、心功能及左室顺应性的影响。方法制作两肾两夹肾性高血压大鼠模型,前胡丙素20 mg.kg-1.d-1,连续灌胃给药9 wk,用离体大鼠工作心脏灌流法检测心功能及左室顺应性,W oessner等报道的方法测定心肌组织羟脯氨酸含量。结果与假手术对照组相比,肾性高血压左室肥厚(LVH)组大鼠CF/HWW和CO/HWW降低29.2%和38.5%,LVSP、-dp/dtm ax分别降低22.8%和43.2%;LV-EDP和T值增高172.9%和187.1%,LVEDP-V曲线左移上抬,左室肌胶原含量增加38.9%。前胡丙素组CF/HWW和CO/HWW比LVH组分别增加23.5%和37.2%,LVSP值和-dp/dtm ax负值较LVH组增加16.0%和42.7%,LVEDP和T值降低38.9%和39.0%,左室LVEDP-V曲线接近正常组水平,左室肌胶原含量降低18.9%,其作用与硝苯地平相似。结论前胡丙素可明显改善两肾两夹肾性高血压大鼠心脏舒张功能,改善心肌顺应性,同时也可改善心脏收缩功能,其作用可能是通过扩张冠状动脉,改善心肌缺血,降低心肌胶原含量而实现。Aim To study the effect of Praeruptorin C (Pra-C) on cardiovascular remodeling, cardiac function and left ventricular diastolic compliance by longterm treatment to two-kidney two-clip (2K2C) renovascular hypertensive rats (RHRs). Methods 2K2C operation was made to SD rats to establish hypertension and left heart hypertrophy (LVH) model, Pra-C 20 mg ·kg^-1· d^-1 was given ig for 9 weeks from the 4th week after 2K2C operation. The isolated working hearts and Langendorff's hearts were made to study the effect of Pra-C on hemodynamics and myocardial com- pliance, and myocardial hydroxyproline content was measured with Woessner's method to evaluate cardiac remodelling. Result Compared to sham-operated group, CF/HWW, CO/HWW and LVSP, -dp/dtmax, (absolute value ) were reduced by 29.2% ,38.5%, 22.8 % ,43.2 % respectively, whereas LVEDP,T value and left ventricle collagen ( represent by hydroxyproline ) content increased by 172.9%, 187.1% ,38.9%, the left ventricular diastolic pressure-volume (P-V) curve was moved to left and upword direction in RHR untreated group. Pra-C treated for 9weeks leadto LVSP and - dp/dtmax ( absolute value) increased 16.0%, 42.7%, while LVEDP and T value and left ventricle collagen content decreased 38.9% ,39. 0% and 18.9% than those in RHR untreated group, and the LVEDP-V curve were shifted to the right and in the up-ward direction. Conclusion These results indicate that Pra-C improved the cardiac relaxation and contractility in 2K2C RHRs, which may be related with increasing the coronary flow and cardic output, decreasing the collagen content in the left ventricular myocardium.
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