【摘要】：目的:尼可地爾是鉀離子通道(ATP sensitive K+channel,KATP)開放劑,臨床已經(jīng)廣泛用于治療缺血性心臟病。當前已有研究運用尼可地爾治療心肌缺血再灌注損傷(myocardial ischemia reperfusion injury,MIRI),但其作用機制尚不清楚。本研究擬探討尼可地爾急性預處理抑制MIRI的作用機制。方法:將75只雄性SD大鼠,運用隨機數(shù)字表法,隨機分為假手術(shù)組、生理鹽水組、尼克地爾A組、尼克地爾B組、尼克地爾C組,每組15只。通過手術(shù)結(jié)扎大鼠冠狀動脈左前降支(left anterior descending coronary arteries,LAD),建立大鼠MIRI模型,假手術(shù)組只穿線不結(jié)扎,缺血30分鐘后,尼可地爾組尾靜脈注射0.2 mL尼可地爾,假手術(shù)組和生理鹽水組尾靜脈0.2 m L生理鹽水,然后再灌注120分鐘。其中,尼可地爾A、B、C組分別給予尼可地爾2.5 mg/kg、5.0 mg/kg、10.0 mg/kg。再灌注結(jié)束后取材,腹主動脈采血取血清,檢測肌酸激酶同工酶(CK-MB)、肌鈣蛋白I(cTn I)、腫瘤壞死因子-α(TNF-α)、白介素-1β(IL-1β)、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)、內(nèi)皮素-1(ET-1)水平;采血后取心臟,蘇木精-伊紅(hemotoxylin and eosin,HE)染色觀察左心室心肌組織病理學改變;2,3,5—氯化三苯基四氮唑(2,3,5-triphenyltetram lium chloride,TTC)染色檢測心肌梗死面積。結(jié)果:與假手術(shù)組比較,生理鹽水組和尼可地爾組大鼠血清CK-MB、cTnI、TNF-α、IL-1β、MDA、ET-1水平升高,NO、SOD水平降低,差異有統(tǒng)計學意義(P0.05);與生理鹽水組比較,尼可地爾組大鼠血清CK-MB、c TnI、TNF-α、IL-1β、MDA、ET-1水平降低,NO、SOD水平升高,差異有統(tǒng)計學意義(P0.05);尼可地爾組間比較,B、C組CK-MB、cTnI、TNF-α、IL-1β、MDA、ET-1水平低于A組,NO、SOD水平高于A組,差異有統(tǒng)計學意義(P0.05),而B、C組之間比較差異無統(tǒng)計學意義(P0.05)。TTC染色結(jié)果顯示尼可地爾組心肌梗死面積小于生理鹽水組,差異具有統(tǒng)計學意義(P0.05);尼可地爾組間比較,B、C組梗死面積小于A組,差異有統(tǒng)計學意義(P0.05),而B、C組之間差異無統(tǒng)計學意義(P0.05)。HE染色結(jié)果顯示假手術(shù)組心肌細胞排列整齊,包膜完整,橫紋清晰,細胞核呈橢圓形;生理鹽水組心肌細胞排列不整齊,橫紋不清晰,細胞水腫,心肌纖維間大量炎細胞浸潤,可見細胞核固縮;尼可地爾A、B、C組也有心肌細胞排列不整齊,橫紋不清晰的表現(xiàn),但程度較輕,心肌纖維間可見不同程度炎細胞浸潤。結(jié)論:尼可地爾單次急性預處理抑制MIRI,它能減少心肌梗死面積,減輕氧化應(yīng)激、炎癥損傷,保護內(nèi)皮功能。其中5mg/kg是較為理想的尼可地爾注射劑量,能夠較大程度地發(fā)揮其抗再灌注損傷的作用。其作用機制可能與尼可地爾具有硝酸鹽特性有關(guān)。
[Abstract]:Objective: nicorandil is a potassium channel (ATP sensitive K channel,KATP opener and has been widely used in the treatment of ischemic heart disease. Nicorandil has been used in the treatment of myocardial ischemia reperfusion injury (myocardial ischemia reperfusion injury,MIRI), but its mechanism is not clear. The aim of this study was to investigate the mechanism of acute pretreatment of nicorandil on inhibition of MIRI. Methods: 75 male SD rats were randomly divided into sham operation group, normal saline group, Nexidil A group, Nexidil B group and Nexidil C group with 15 rats in each group. Rat model of MIRI was established by ligating left anterior descending branch of coronary artery (left anterior descending coronary arteries,LAD). After 30 minutes of ischemia, nicodil was injected into the tail vein of nicorandil group with 0.2 mL nicodil. The caudal vein of sham-operated group and saline group was 0.2 mL saline, then perfused for 120 minutes. In group C, nicorandil was given for 2.5 mg/kg,5.0 mg/kg,10.0 mg/kg., respectively. After reperfusion, serum samples were collected from abdominal aorta. Creatine kinase isoenzyme (CK-MB), troponin I (cTn I), tumor necrosis factor- 偽 (TNF- 偽), interleukin-1 尾 (IL-1 尾) were detected. Superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (no), (NO), endothelin-1 (ET-1); The left ventricular myocardial histopathological changes were observed by hematoxylin and eosin (hemotoxylin and eosin,HE staining, and myocardial infarction size was detected by 2-titriphenyltetramethyl lium chloride,TTC staining. Results: compared with sham operation group, the serum levels of CK-MB,cTnI,TNF- 偽, IL-1 尾, MDA,ET-1 in normal saline group and nicorandil group were increased and NO,SOD level was decreased (P0.05). Compared with normal saline group, the serum levels of CK-MB,c TnI,TNF- 偽, IL-1 尾, MDA,ET-1 in nicorandil group decreased and NO,SOD level increased (P0.05). The levels of CK-MB,cTnI,TNF- 偽, IL-1 尾, MDA,ET-1 in group B C were lower than those in group A, and NO,SOD levels were higher than those in group A (P0.05). There was no significant difference between group C (P0.05). TTC staining results showed that the size of myocardial infarction in nicorandil group was smaller than that in saline group, the difference was statistically significant (P0.05); The infarct size in group B C was smaller than that in group A (P0.05), but there was no significant difference between group B and C (P0.05). HE staining showed that myocardial cells were arranged neatly in sham operation group. The capsule was intact, the striation was clear and the nucleus was elliptic. In the saline group, the myocardial cells were not arranged neatly, the striations were not clear, the cells were edema, a large number of inflammatory cells were infiltrated between the myocardial fibers, and the nuclei were pyknosis. In group C, the arrangement of cardiomyocytes was irregular, the striation was not clear, but the degree was light, and inflammatory cell infiltration could be seen in different degree between myocardial fibers. Conclusion: single acute pretreatment with nicorandil can reduce myocardial infarction size, reduce oxidative stress, inflammatory injury and protect endothelial function. Among them, 5mg/kg is an ideal dose of nicorandil, which can play an important role in anti-reperfusion injury. The mechanism may be related to the nitrates of nicordil.
【學位授予單位】：湖北醫(yī)藥學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R542.22

【參考文獻】

相關(guān)期刊論文 前5條

1 Lian-Yue Guan;Pei-Yao Fu;Pei-Dong Li;Zhuo-Nan Li;Hong-Yu Liu;Min-Gang Xin;Wei Li;;Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide[J];World Journal of Gastrointestinal Surgery;2014年07期

2 Qian Hu;Jiong Chen;Chao Jiang;Heng-Fang Liu;;Effect of peroxisome proliferator-activated receptor gamma agonist on heart of rabbits with acute myocardial ischemia/reperfusion injury[J];Asian Pacific Journal of Tropical Medicine;2014年04期

3 Maria-Giulia Perrelli;Pasquale Pagliaro;Claudia Penna;;Ischemia/reperfusion injury and cardioprotective mechanisms:Role of mitochondria and reactive oxygen species[J];World Journal of Cardiology;2011年06期

4 侯春麗;張冬梅;侯學紅;楊少軍;;大鼠急性心肌梗死模型制備及對心功能影響的實驗研究[J];寧夏醫(yī)科大學學報;2010年09期

5 楊建業(yè);安慶寶;張迎春;唐俊明;郭凌鄖;黃永章;王家寧;;液氮冷凍大鼠左冠狀動脈前降支中上1/3所支配區(qū)域建立心肌梗死模型[J];中國比較醫(yī)學雜志;2008年03期

，

本文編號：2387150