【摘要】： 目的:本實(shí)驗(yàn)研究ST-1灌胃預(yù)處理對(duì)麻醉大鼠心肌缺血再灌注損傷的保護(hù)作用,對(duì)其作用機(jī)制進(jìn)行初步探討,并與甜菊苷6種衍生物進(jìn)行藥效學(xué)的比較。 方法:健康成年大鼠(300±50g)隨機(jī)分成偽手術(shù)組、模型對(duì)照組、ST-1預(yù)處理組、冠心丹參片預(yù)處理組和甜菊苷衍生物組,每組12只,藥物在心肌缺血前60 min灌胃給予。大鼠開(kāi)胸后結(jié)扎左冠狀動(dòng)脈前降支30 min再通90 min以形成缺血再灌注模型。連續(xù)觀察各組鼠動(dòng)態(tài)血流動(dòng)力學(xué)指標(biāo):MBP、LVSP、LVDP’、LVEDP和±dp/dtmax等,并記錄心律失常(室速,VT和室顫,VF)情況;測(cè)定生物化學(xué)指標(biāo):再灌注末血清乳酸脫氫酶(LDH)和肌酸激酶(CK)的活性;觀察心肌組織形態(tài)學(xué)變化,并用免疫組化方法測(cè)定核因子κB(NFκB)、Bcl-2和環(huán)氧酶2(COX-2)的活性。 結(jié)果:大鼠心肌缺血再灌注可引起心功能、生化和組織學(xué)損傷。ST-1 2.5、5.0 mg·kg-1灌胃和冠心丹參片200 mg·kg-1灌胃預(yù)處理可有效減輕缺血再灌注引起的心功能損傷。ST-1組和冠心丹參片組左室舒縮功能指標(biāo)均明顯高于缺血再灌注模型對(duì)照組;心率和血壓變化與模型對(duì)照組間無(wú)顯著性差異;缺血再灌注期VT和VF發(fā)生率、再灌注末血清LDH和CK活性均明顯低于模型對(duì)照組對(duì)應(yīng)值。心肌光鏡觀察表明:ST-1組心肌組織形態(tài)學(xué)損傷明顯輕于模型對(duì)照組,并顯示與ST-1劑量相關(guān)。免疫組織化學(xué)觀察表明:ST-1組心肌組織的NFκB和COX-2的表達(dá)活性明顯低于模型對(duì)照組,而B(niǎo)cl-2的表達(dá)活性明顯高于模型對(duì)照組。本實(shí)驗(yàn)尚不能證實(shí)我校自行合成的6種甜菊苷系列衍生物灌胃預(yù)處理具有相似于ST-1的抗心肌缺血再灌注損傷作用。 結(jié)論:本實(shí)驗(yàn)證實(shí)ST-1灌胃與靜脈注射預(yù)處理具有一致的抗麻醉大鼠心肌缺血再灌注損傷作用,該作用可能與抗炎、抗心肌細(xì)胞凋亡有關(guān)。
[Abstract]:Aim: to study the protective effect of ST-1 preconditioning on myocardial ischemia-reperfusion injury in anesthetized rats and its mechanism, and to compare its pharmacodynamics with 6 kinds of stevioside derivatives. Methods: healthy adult rats (300 鹵50 g) were randomly divided into sham operation group, model control group, Guanxin Danshen tablet preconditioning group and stevioside derivative group, 12 rats in each group. The model of ischemia reperfusion was established by ligating the anterior descending branch of the left coronary artery for 90 min after thoracotomy. LVEDP and 鹵dp/dtmax were observed continuously, and the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum were measured at the end of reperfusion, and the arrhythmias (ventricular tachycardia VT and ventricular fibrillation VF) were recorded, and serum lactate dehydrogenase (LDH) and creatine kinase (CK) were measured at the end of reperfusion. The changes of myocardial histomorphology were observed and the activities of NF- 魏 B (NF 魏 B, Bcl-2 and cyclooxygenase-2 (COX-2) were determined by immunohistochemical method. Results: myocardial ischemia-reperfusion induced cardiac function in rats. The indexes of left ventricular systolic and diastolic function in the myocardial ischemia reperfusion group and Guanxin Danshen tablet group were significantly higher than those in the ischemic reperfusion model group and the Guanxin Danshen tablet group and Guanxin Danshen tablet group, respectively. There was no significant difference in heart rate and blood pressure between the model group and the model control group, but the incidence of VT and VF during ischemia-reperfusion and the activities of serum LDH and CK at the end of reperfusion were significantly lower than those in the model control group. Myocardial light microscopy showed that the myocardial histomorphologic damage in the group of w ST-1 was significantly less than that in the model control group and was correlated with the dose of ST-1. Immunohistochemical observation showed that the expression of NF 魏 B and COX-2 in the myocardium of the group of w ST-1 was significantly lower than that of the model control group, while the activity of Bcl-2 was significantly higher than that of the model control group. This experiment can not confirm that the preconditioning of 6 kinds of stevioside derivatives has similar effects on myocardial ischemia-reperfusion injury as ST-1. Conclusion: this study demonstrated that ST-1 administration and intravenous preconditioning had the same effect on myocardial ischemia-reperfusion injury in anesthetized rats, which might be related to anti-inflammation and anti-apoptosis of cardiomyocytes.
【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類號(hào)】：R363

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相關(guān)期刊論文 前4條

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本文編號(hào)：2229482