【作者】 杜立建；

【导师】 吴俊喜；

【作者基本信息】 河北医科大学 ， 中医内科学， 2007， 硕士

【摘要】 近年来,干预急性心肌梗死(AMI)后心室重构(VR)已成为冠心病急性心肌梗死研究领域中备受关注的热点,但中药对AMI后VR的研究仍较少有报道。中药方剂强心灵(QXL)是以中医理论中益气活血化瘀治则组成的验方,经临床大量病例验证,具有逆转AMI后VR的作用。本研究通过实验与临床两个方面进一步探讨其作用机制。实验研究目的:探讨强心灵对冠状动脉结扎所致AMI大鼠VR的干预机制。方法:选择清洁级健康Wistar大鼠85只,随机分为5组,每组17只,采取冠状动脉结扎造成AMI模型,术后死亡20只,总死亡率23.6%,术后24小时成功存活的大鼠,假手术组(开胸后只挂线而不结扎冠状动脉)(13只),模型对照组(15只),卡托普利组(11只),强心灵小剂量(QXLmin)(14只)和强心灵大剂量组(QXLmax)(12只),模型组及假手术组予以相应的生理盐水,其它组均予口服给药治疗。4周后处死,放射免疫法测血浆AngⅡ,SOD含量,计算左心室质量指数,取心尖组织,进行苏木素-伊红(HE)染色,光镜下观察病理形态学改变,并采用ABC染色测TGF-β1的表达量。用HPIAS-1000高清晰彩色病理图文报告分析系统分析,检测每张切片5个高倍视野下阳性细胞的吸光值(OD),计算其均数为TGF-β1相对含量。结果:(1)血浆AngⅡ,SOD含量,模型组及各给药组与假手术组相比AngⅡ水平较高(p<0.01),各给药组较模型组有下降趋势(p<0.01),其中QXLmax组较卡托普利组及QXLmin组更低(p<0.05)。SOD:模型组及各给药组SOD水平较假手术组降低(p<0.01),QXLmax组及QXLmin组较模型组有升高趋势(p<0.01),卡托普利组与模型组间SOD值差异无统计学意义。(2)左心室质量指数:模型组较假手术组显著升高(p<0.01),各给药组较假手术组有升高趋势有统计学意义(p<0.05),QXLmax组较QXLmin组及卡托普利组降低,其差异有统计学意义(p<0.05),后两组之间差异无统计学意义(p>0.05)。(3)组织病理损伤:假手术组心肌细胞排列整齐,未见明显变性及坏死,模型组见心肌组织呈灶性坏死,偶见灶间相互连接,大量胶原纤维增生,呈大斑片状,部分心肌细胞较假手术组,明显增大,胞浆染色深。卡托普利组及QXLmin组健存心肌细胞周围胶原组织明显减少,QXLmax组病理改变最轻,偶有少量胶原纤维增生。(4)TGF-β1表达:与假手术组比较,其余各组均有不同程度表达,其中模型组较其余各组表达最高(p<0.01),QXLmax组较QXLmin组及卡托普利组表达低(p<0.01),在数值上,QXLmin组较卡托普利组表达低,但无统计学意义(p>0.05)。统计方法:采用Spss11.5软件统计数据。结论:强心灵具有逆转大鼠AMI后VR的作用。强心灵可通过降低血浆AngⅡ水平,增加SOD活性,降低左心室质量指数,降低心肌组织TGF-β1表达,从而减少氧自由基对细胞的损伤,减轻胶原沉积,延缓纤维化的发展过程,逆转AMI后VR的发生。临床研究目的:观察强心灵对AMI后患者VR的干预机制。方法:选择AMI患者90例,随机分为对照组43例,强心灵治疗组47例,疗程4周。对照组常规使用扩张冠脉,增加冠脉血流量,及时处理严重并发症。治疗组在常规治疗基础上使用强心灵。测定两组治疗前后4周临床疗效;血浆血管紧张素Ⅱ(AngⅡ),血浆Ⅲ型前胶原氨基端肽(PⅢNP),血清转化生长因子-β1(TGF-β1)及血管超氧化物歧化酶(SOD)含量变化;左室舒张末容积指数(EDVI),左室收缩末容积指数(ESVI),左室射血分数(EF)和室壁运动指数(WMSI);安全性观察。统计方法:采用Spss11.5软件统计数据。结果:与治疗前相比,对照组和治疗组均取得明显效果(p<0.05);两组均可降低血浆AngⅡ,PⅢNP及血清TGF-β1,增加SOD活力,明显改善EDVI,ESVI,EF,WMSI较开始明显改善(p<0.05),但治疗组在改善程度上有差异(p<0.05)。结论:强心灵可逆转AMI后VR的发生。更多还原

【Abstract】 In recent years, interfering Ventricular Remodeling (VR) after Acute Myocardial Infarction (AMI) has been the hot Point which has been paid more attention in the scope of coronary atherosclerotic heart disease (CHD), but there are few records in the scope of Chinese traditional medicine QIANG XIN LING (QXL) a kind of effecting traditional Chinese medicine, is established on the traditional medical chicory of Nourish Qi, activate blood circulation and Hua Yu. Proved by a great deal of clinical evidence, plays a role in reversing VR after AMI. The research is through two aspects of experimental and clinical to further explore its functional mechanism.Experimental ResearchObjective: To explore the interfering mechanism of QXL to VR after AMI which caused by legation of rats coronary artery .Methods: 85 healthy male Wistar rats were selected and randomly divided into five groups, each group had 17 rats. Rat models of AMI were established by ligation of left coronary artery, 24 hours after the operation, there were 20 rats died and the operative mortability of the curgical procedure was 23.6%. Among the survival rats, QXLmas (n=12), QXLmin (n=14) and Captopril group (n=11) were all treated with medicine by intragastric administration, while Model group (n=15) and Sham-operation group (n=13) (pericardium was opened without the ligation of the left coronary artery). Received the same does saline. Four weeks later, all rats were killed. Radvoimmunoassay was taken to determine AngⅡ(AngiotensinⅡ) and SOD(Superoxide Dismutase). LVMI(left ventricular mass index) was calculated and HE staining was employed to observe the Pathological Changes of left ventricular structure the myocardium, ABC Staining was to detect the expression of TGF-β1(Tranforming Growth Factor-β1)in the myocardium. Statistical method: The data was statistied with the soft of Spss 11.5.Results:⑴AngⅡ,SOD After four weeks treatment the contents of AngⅡof Model group and drug treatment groups were significantly higher than Sham-operation group (P<0.01), drug treatments groups` contents were lower than Model l group(P<0.05 or P<0.01). QXLmas was much lower than Captopril group and QXLmin group (P<0.01), the last two groups’difference has no statistical significance(P≥0.05).SOD: The contents of Model group and drug treatment groups were lower than Sham-operation group (P<0.01).the last there groups were higher than Model group(P<0.05) QXLmas was highest among the last there groups, the difference between QXLmas and captopril group had statistical significance (P<0.01), the content of SOD of QXLmin was also higher than Captopril group(P<0.05). LVMI: The last four groups, whose LVMI was higher than Sham- operation group (P<0.05) Captopril group, QXLmin and QXLmas were lower than Model group, the difference had statistical significance(P≥0.05). the last three groups` LVMI were lower than Model l group (P<0.05 or P<0.01). Compared with captopril group, the LVMI QXLmin was lower (P<0.05) and QXLmas was the lowest (P<0.01). TGF-β1 : Expression of TGF-β1 in Sham-operation was lower, as well TGF-β1 were detected expressed in all other groups and were higher than Sham-operation (P<0.01). TGF-β1 expressed highest in Model group (P<0.05 or P<0.01). the amount of expression in QXLmin was much lower than Captopril group, the difference had statistical significance (P<0.01).Conclusion: QXL can reverse VR after hats` AMI which caused by ligation of rats` coronary artery.Clinical ResearchObjective: To observe the interfering mechanism of QXL to the patiente’s VR after AMI.Methods: 90 patients with AMI were selected and random divided into Control group (n=43) and Treatment group (n=47). All were treated with routine method of dilating coronary artery increasing the coronary artery blood circulation and treating the serious diseases happened at the same time on time. Treatment group was added the Chinese traditional medicine QXL beside the same method. After 4 weeks, observe the clinical effective, investigate the contents of AngⅡ,PⅢNP(Propeptide of type ProcollagenⅢ),TGF-β1 and SOD between before and after treatment, observe the difference of EDVI(end-diastolic volume index), ESVI(end-systolic volume index), EF(ejection fraction) and WMSI(wall motion score index) and the security. Compared with before the treatment, the contents of AngⅡ,PⅢNP,TGF-β1 significantly decreased, while the SOD increased .EDVI, ESVI and ET obviously improved at the same time. WMSI was decreased but Treatment group had more effect. (P<0.05 or P<0.01). Statistical method: The data was statistied with the soft of Spss 11.5.Results: Treatment group had more significant effect than Control group. Amory 47 patients of Treatment group, there were 21 patients had significant effect (44%), 38.5% of the patients’clinical symptom was changed better and 8% had no effect. The amount of effective of the group was 83.0% which was higher than control group.Conclusion: QXL can reverse the process of VR after AMI.更多还原