动脉粥样硬化模型大鼠ADP与炎性因子表达及中药对其调控的机制研究

【作者】 常炳堃；

【导师】 吕晓东；

【作者基本信息】 辽宁中医药大学 ， 中医内科学， 2011， 硕士

【摘要】 目的:通过对动脉粥样硬化模型大鼠治疗,探讨脂联素与炎性因子表达水平的相关性,并观察通脉化浊汤不同剂量对其的影响。材料与方法:选取SD大鼠216只随机分为六组,空白对照组、模型组、通脉化浊汤二倍剂量组、正常剂量组、1/2剂量组、血脂康对照组,各组大鼠(除正常组大鼠外)在给予维生素D370万IU/kg(3天内灌胃)后,饲喂高脂饮食,以造动脉粥样硬化模型,正常组大鼠在给予同体积生理盐水灌胃后饲喂普通饲料;造模成功后给予改换普通饲料喂养,同时进行药物治疗,通脉化浊汤高、中、低剂量组(分别含生药量2.79g/ml、1.395g/ml、0.6975g/ml)分别给予对应剂量汤剂2ml/200g日一次灌胃给药,中药对照组(含血脂康0.0108g/ml)给予血脂康胶囊水溶液2ml/200g日一次灌胃给药,正常组及模型组给予同等体积的生理盐水,于给药后1、2、4周各组随机抽取12只大鼠,乌拉坦麻醉,腹主动脉取血,检测血脂、ADP、IL-6、CRP,摘取主动脉,备做病理切片,摘取心尖组织,备做RT-PCR。结果:通过血清学检测血脂指标可见,模型组在各个时间段TC、TG、LDL含量均明显高于空白对照组,HDL含量明显低于空白对照组,通过一周的治疗后各治疗组TC、TG、LDL含量均有所降低,HDL也有一定的升高,继续治疗至第四周后,血脂各项指标已经接近空白对照组,且无显著差异。治疗过程中通脉化浊汤正常剂量组及二倍剂量组与血脂康对照组间血脂水平无显著差异。模型组各个时间段的炎症因子指标IL-6和CRP明显高于空白组,ADP明显低于空白组,通过四周的治疗后各治疗组IL-6和CRP逐渐降低,ADP逐渐升高,于治疗后第二周开始与模型组产生明显差异并继续加深。通过光镜观察病理切片可见,模型组大鼠动脉血管明显增厚,表面纤维帽呈不同程度的玻璃样变;病灶深部可见无定型的坏死崩溃物,其中含有胆固醇结晶(呈针状或梭形空隙),通过中药汤剂通脉化浊汤的治疗后,动脉粥样硬化程度减轻,管壁变薄,胶原纤维增生明显。通过RT-PCR技术检测可见,模型组在各个时间段TNF-α含量均明显高于空白对照组,ADP含量明显低于空白对照组,通过四周的治疗后各治疗组TNF-α逐渐降低,ADP逐渐升高,于治疗后第二周开始与模型组产生明显差异并继续加深。结论:通脉化浊汤能够明显降低血清TC、TG、LDL含量,升高HDL含量,具有良好的降脂、保护血管内皮、稳定斑块的作用;通脉化浊汤可有效的降低TNF-α、IL-6及CRP,能够良好的对动脉粥样硬化进行抗炎治疗,从而对动脉粥样硬化的发生发展产生重要影响;通脉化浊汤能够明显升高ADP,通过改善血管内皮功能,减少黏附因子的表达,抑制巨噬细胞产生细胞因子并减弱其胞吞作用及抑制血管损伤后平滑肌细胞的增殖从而达到抑制、治疗动脉粥样硬化的作用;通脉化浊汤通过降低血脂含量,抑制炎症因子的表达,提高ADP水平从而达到抗动脉粥样硬化发生机制的作用。更多还原

【Abstract】 Purpose:To explore the relevance between expression level of adiponectin (ADPN) and tumor necrosis factorα(TNF-α).Material and method:216 wistar rats were randomly divided into six groups: control group, model group, Tōng Mài HuàZhuóTāng high dose group,Tōng Mài HuàZhuóTāng middle dose group, Tōng Mài HuàZhuóTāng low dose group, and Chinese medicinals control group. The atherosclerosis model was induced by feeding the rats with cholesterol-rich fodder. Then the medicinals were administered on these rats, 12 of which were executed in the fourth, sixth and eighth weeks counted from the day of administration. After the relevant tissues for research were taken, the expression levels of ADP and TNF-αin myocardial cell were tested using the technology of RT-PCR.Results:1. There is a positive relevance between expression level of ADPN and TNFα,2. and also there is an inhibitory effect of ADP on TNF-α. Above all,。3. recipes of Chinese medicine have clear regulatory effects on the expression of ADP.Conclusion:1. Tōng Mài HuàZhuóTāng is very promising both clinically.2. practically in its effect on controlling.3. treating atherosclerosis by promoting the level of ADP that inhibits the expression of TNF-α.更多还原