CAJ | 학술논문

目的探讨异丙酚对肝缺血再灌注大鼠心肌损伤的影响及磷脂酰肌醇-3激酶/蛋白质丝氨酸苏氨酸激酶(PI3K/Akt)信号通路在其中的作用.方法清洁级雄性SD大鼠102只,体重250～280g,采用结扎肝蒂30 min后再灌注的方法制备肝缺血再灌注模型.随机分为5组:假手术组(S组,n=6)仅分离肝门,不结扎;缺血再灌注组(I/R组,n=30)制备肝缺血再灌注模型;异丙酚组(P组,n=30)缺血前10 min股静脉注射异丙酚12 mg/k异的负荷剂量,随后以30 mg·kg-1·h-1的速率静脉输注直至处死;异丙酚+PI3K抑制剂组(P+LY组,n=18)缺血前10 min股静脉注射PI3K特异性抑制剂LY294002 1.5mg/kg(溶于二甲亚砜0.5 ml);溶剂对照组(P+DMSO组,n=18)缺血前10 min股静脉注射二甲亚砜0.5 ml.I/R组和P组于再灌注即刻、30、60、120和240 min(T1-55)时,P+LY组和P+DMSO组于T3-5时取6只大鼠,处死后快速取左心室壁心肌组织,测定总Akt(t-Akt)和磷酸化Akt(p-Akt),并于T3时测定Bcl-2的表达和心肌细胞凋亡情况,取肝左外叶组织,光镜下观察肝组织病理学结果.S组于T1相应时点处死大鼠,测定上述指标.结果与S组比较,其余各组心肌p-Akt表达水平和心肌细胞凋亡率升高(P＜0.05),P+LY组心肌Bcl-2表达差异无统计学意义(P＞0.05),其他各组心肌Bcl-2表达均上调(P＜0.05);与I/R组比较,P组和P+DMSO组心肌p-Akt和Bcl-2表达上调,心肌细胞凋亡率降低(P＜0.05),P+LY组上述指标差异无统计学意义(P＞0.05);与P组比较,P+LY组心肌p-Akt和Bcl-2表达下调,心肌细胞凋亡率升高(P＜0.05),P+DMSO组上述指标差异无统计学意义(P＞0.05);各组心肌t-Akt表达比较差异无统计学意义(P＞0.05).P组和P+DMSO组肝组织病理学损伤较I/R组和P+LY组减轻.结论异丙酚可减轻大鼠肝缺血再灌注诱发心肌损伤,该作用与激活PI3K/Akt信号通路有关.
목적 탐토이병분대간결혈재관주대서심기손상적영향급린지선기순-3격매/단백질사안산소안산격매(PI3K/Akt)신호통로재기중적작용.방법 청길급웅성SD대서102지,체중250～280g,채용결찰간체30 min후재관주적방법제비간결혈재관주모형.수궤분위5조:가수술조(S조,n=6)부분리간문,불결찰;결혈재관주조(I/R조,n=30)제비간결혈재관주모형;이병분조(P조,n=30)결혈전10 min고정맥주사이병분12 mg/k이적부하제량,수후이30 mg·kg-1·h-1적속솔정맥수주직지처사;이병분+PI3K억제제조(P+LY조,n=18)결혈전10 min고정맥주사PI3K특이성억제제LY294002 1.5mg/kg(용우이갑아풍0.5 ml);용제대조조(P+DMSO조,n=18)결혈전10 min고정맥주사이갑아풍0.5 ml.I/R조화P조우재관주즉각、30、60、120화240 min(T1-55)시,P+LY조화P+DMSO조우T3-5시취6지대서,처사후쾌속취좌심실벽심기조직,측정총Akt(t-Akt)화린산화Akt(p-Akt),병우T3시측정Bcl-2적표체화심기세포조망정황,취간좌외협조직,광경하관찰간조직병이학결과.S조우T1상응시점처사대서,측정상술지표.결과 여S조비교,기여각조심기p-Akt표체수평화심기세포조망솔승고(P＜0.05),P+LY조심기Bcl-2표체차이무통계학의의(P＞0.05),기타각조심기Bcl-2표체균상조(P＜0.05);여I/R조비교,P조화P+DMSO조심기p-Akt화Bcl-2표체상조,심기세포조망솔강저(P＜0.05),P+LY조상술지표차이무통계학의의(P＞0.05);여P조비교,P+LY조심기p-Akt화Bcl-2표체하조,심기세포조망솔승고(P＜0.05),P+DMSO조상술지표차이무통계학의의(P＞0.05);각조심기t-Akt표체비교차이무통계학의의(P＞0.05).P조화P+DMSO조간조직병이학손상교I/R조화P+LY조감경.결론이병분가감경대서간결혈재관주유발심기손상,해작용여격활PI3K/Akt신호통로유관.
Objective To investigate the effect of propofol on myocardial injury induced by hepatic ischemia/reperfusion (I/R) in rats and the role of PI3K/Akt signaling pathway. Methods One hundred and two male SD rats weighing 250-280 g were randomly divided into 5 groups: Ⅰ sham operation group (group S, n =6), ⅡI/R group ( n = 30), Ⅲ propofol group (group P, n = 30), Ⅳ propofol + LY294002 group (group P+ LY, n =18), and Ⅴ propofol + dimethylsulfoxide group (group P+ DMSO, n = 18). Hepatic I/R was produced by occlusion of hepatic pedicle for 30 min followed by reperfusion in group Ⅱ - Ⅴ. Propofol 12 mg/kg, propofol 12mg/kg + LY294002 (a specific PI3K inhibitor) 1.5 mg/kg, and propofol 12 mg/kg + DMSO 0.5 ml were injected I.v.via femoral vein at 10 min before ischemia in group Ⅲ -Ⅴ respectively, and then propofol was infused I.v. At a rate of 30 mg· kg- 1 · h - 1 and the administration was stopped before the rats were sacrificed in group Ⅲ - Ⅴ . At 0,30, 60, 120, and 240 min of reperfusion (T1-5) in group Ⅱ and Ⅲ , and at T3.5 in group Ⅳ and Ⅴ , six rata were sacrificed and myocardial tissues were taken for determination of the total Akt (t-Akt) and phosphorylated Akt (p-Akt) expression and Bcl-2 expression and apoptosis were detected at T3. The hepatic tissues were taken for microscopic examination. The rats were sacrificed at T1 and the parameters mentioned above were detected in group Ⅰ . Results Compared with group Ⅰ , p-Akt expression and apoptosis rate were significantly increased in the other4 groups, and Bcl-2 expression was up-regulated in group Ⅱ , Ⅲ and Ⅴ (P ＜ 0.05). Compared with group Ⅱ , p-Akt and Bcl-2 expression was up-regulated, and the apoptosis rate was significantly decreased in group Ⅲand Ⅴ ( P ＜ 0.05). Compared with group Ⅲ , p-Akt and Bcl-2 expression was down-regulated, and the apoptosis rate was significantly increased in group Ⅳ ( P ＜ 0.05). The microscopic examination showed that the injury to the hepatic tissues was less severer in group Ⅲ and Ⅴ than in group Ⅱ and Ⅳ. Conclusion Propofol can attenuate myocardial injury induced by hepatic I/R in rats by activation of PI3K/Akt signaling pathway.