机构地区:[1]遵义医学院珠海校区病理学与病理生理学教研室,珠海519041 [2]遵义医学院珠海校区计算机教研室,珠海519041 [3]枣庄科技职业学院医学技术系,滕州277500
出 处:《中药药理与临床》2012年第5期71-75,共5页Pharmacology and Clinics of Chinese Materia Medica
基 金:珠海市科技局资助项目(No.PC20071045);贵州省科技厅资助项目(No.黔科合J字[2008]2317);贵州省高层次人才科研条件特助经费资助项目(No.TZJF-2008年58号)
摘 要:目的:探讨葡萄籽原花青素(GSP)对肾血管性高血压(RH)大鼠血管重塑的影响。方法:采用两肾一夹法建立RH大鼠模型,并设立假手术组。术后2周,选取鼠尾动脉收缩压升至130mmHg以上的大鼠28只为RH大鼠,随机分为4组:高血压模型组,GSP低剂量治疗组(50mg/kg);GSP高剂量治疗组(200mg/kg)和卡托普利阳性对照治疗组(30mg/kg)。治疗6周后,分别测定各组大鼠尾动脉收缩压,苏木精-伊红染色法染色并观察胸主动脉形态,测量中膜平滑肌层数,中膜厚度(MT),管腔内径(LD)及MT/LD等血管重塑形态学参数。ELISA法测量腹主动脉血管组织中内皮素(ET)的含量,Western blotting法检测腹主动脉血管组织中ERK1/2蛋白的表达水平。结果:治疗6周后,与假手术组比较,高血压模型组大鼠的尾动脉收缩压,MT、MT/LD,ET含量,中膜平滑肌层数,ERK1/2蛋白表达水平明显升高;胸主动脉内膜不完整,中膜平滑肌增多,管壁明显增厚,而LD减小。与高血压模型组相比,GSP低(50mg/kg)、高(200mg/kg)剂量均能降低RH大鼠的尾动脉收缩压、MT和MT/LD,减少ET的含量、中膜平滑肌层数的增多,和ERK1/2的蛋白表达水平,亦可以使内膜不完整、,中膜平滑肌增多、管壁增厚及LD减小的现象得到缓解,其中,以高剂量(200mg/kg)GSP治疗组的作用尤为明显,与卡托普利(30mg/kg)治疗组的作用相当。结论:GSP不仅能显著降低RH大鼠尾动脉收缩压,而且对血管重塑有缓解作用,其机制可能与GSP能降低腹主动脉中ET的含量和ERK1/2的蛋白表达有关。Objective:To investigate the effect of grape seed procyanidin(GSP) on vascular remodeling in renovascular hypertensive(RH) rats.Methods:The RH model was established by two-kidney one clip(2K1C) method.Two weeks after operation,28 rats were selected according to the increased tail systolic pressure above 130mmHg and randomly divided into 4 groups(n=7):renovascular hypertensive model group(RH model);low GSP treated group(low GSP,50mg/kg/d);high GSP treated group(high GSP,200mg/kg/d) and captopril treated group(captopril,30mg/kg/d).Meanwhile,7 rats with sham operation were served as controls.Tail systolic pressure,the structural of thoracic aortic,the parameters of vascular remodeling,including amount of medial smooth muscle layers,medial thickness(MT),luminal diameter(LD),ratio of MT/LD were measured through the methods of tail-cuff or HE staining after 6 weeks treatment.ELISA were used to detect the content of endothelin(ET) in aortic tissue.Western blotting was performed to detect the expression level of extracellular signalregulated kinase 1/2(ERK1/2) protein in aortic tissue.Results:compared with control group,the tail systolic pressure,MT,the ratio of MT/LD,ET,layers of medial smooth muscle and the level of ERK1/2 protein in aorta were significantly increased;thoracic aortic intima wasn't smooth,medial smooth muscle proliferation,the vascular wall thickening and LD decreased were found.Low(50mg/kg) and high(200mg/kg) GSP can reduce the tail systolic pressure,MT,the ratio of MT/LD,ET,layers of medial smooth muscle and the level of ERK1/2 protein in aorta markedly,make thoracic aortic intima smooth,relieve medial smooth muscle proliferation,the vascular wall thickening and LD decreased.These effects are more notable in high GSP(200mg/kg) group,equal to captopril(30mg/kg) treated group.Conclusion:GSP can not only decrease tail systolic pressure significantly of RH rats,but also attenuated arterial vascular remodeling effectively by decrea
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