CAJ | 학술논문

目的评价磷脂酰肌醇-3-激酶-蛋白质丝氨酸苏氨酸激酶(PI3K-Akt)信号通路在二氮嗪后处理减轻大鼠心肌缺血再灌注损伤中的作用.方法成年雄性SD大鼠36只,体重250～300 g,采用随机数字表法,将其随机分为4组(n=9):心肌缺血再灌注组(I/R组)、二氮嗪组(D组)、PI3K抑制剂渥蔓青霉素组(W组)和二氮嗪复合渥蔓青霉素组(DW组).采用结扎大鼠左冠状动脉前降支30min再开放120 min的方法制备心肌缺血再灌注模型.缺血25 min时,4组分别经股静脉输注0.1％二甲基亚砜、二氮嗪0.47 mg·kg-1·min-、渥蔓青霉素1 μg·kg-1 ·min-1和二氮嗪0.47 mg·kg-1·min-1,其中DW组于给予二氮嗪前5min静脉输注渥蔓青霉素1μg·kg-·min -,药物输注时间均为15 min.再灌注120 min时经左心室采集血样,测定血浆乳酸脱氢酶(LDH)活性；取心肌组织,测定心肌梗死面积、细胞凋亡率、Bcl-2和Bax的表达,并计算Bcl-2与Bax的比值(Bcl-2/Bax比).结果与I/R组比较,D组和DW组血浆LDH活性、心肌梗死面积及细胞凋亡率降低,心肌组织Bcl-2表达上调,Bax表达下调,BcL2/Bax比升高(P＜0.05或0.01),W组上述指标差异无统计学意义(P＞0.05)；与D组比较,DW组血浆LDH活性、心肌梗死面积以及细胞凋亡率降低,心肌组织Bcl-2表达下调,Bax表达上调,Bcl-2/Bax比降低(P＜0.05或0.01).结论 PI3K-Akt信号通路参与了二氮嗪后处理减轻大鼠心肌缺血再灌注损伤.
목적 평개린지선기순-3-격매-단백질사안산소안산격매(PI3K-Akt)신호통로재이담진후처리감경대서심기결혈재관주손상중적작용.방법 성년웅성SD대서36지,체중250～300 g,채용수궤수자표법,장기수궤분위4조(n=9):심기결혈재관주조(I/R조)、이담진조(D조)、PI3K억제제악만청매소조(W조)화이담진복합악만청매소조(DW조).채용결찰대서좌관상동맥전강지30min재개방120 min적방법제비심기결혈재관주모형.결혈25 min시,4조분별경고정맥수주0.1％이갑기아풍、이담진0.47 mg·kg-1·min-、악만청매소1 μg·kg-1 ·min-1화이담진0.47 mg·kg-1·min-1,기중DW조우급여이담진전5min정맥수주악만청매소1μg·kg-·min -,약물수주시간균위15 min.재관주120 min시경좌심실채집혈양,측정혈장유산탈경매(LDH)활성；취심기조직,측정심기경사면적、세포조망솔、Bcl-2화Bax적표체,병계산Bcl-2여Bax적비치(Bcl-2/Bax비).결과 여I/R조비교,D조화DW조혈장LDH활성、심기경사면적급세포조망솔강저,심기조직Bcl-2표체상조,Bax표체하조,BcL2/Bax비승고(P＜0.05혹0.01),W조상술지표차이무통계학의의(P＞0.05)；여D조비교,DW조혈장LDH활성、심기경사면적이급세포조망솔강저,심기조직Bcl-2표체하조,Bax표체상조,Bcl-2/Bax비강저(P＜0.05혹0.01).결론 PI3K-Akt신호통로삼여료이담진후처리감경대서심기결혈재관주손상.
Objective To investigate the role of phosphatidylinositol 3-kinase/protein-serine-threonine kinases (PI3K-Akt) signal pathway in the protection of myocardium against ischemia-reperfusion (I/R) injury by diasoxide postconditioning in rats.Methods Thirty-six male SD rats weighing 250-300 g were randomly divided into 4 groups using random number table (n =9 each):group I/R; group diazoxide (group D); group wortmannin (PI3K inhibitor) (group W) and group wortmannin + diazoxide (group WD).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 4 ml/kg,intubated and mechanically ventilated.Myocardial I/R was produced by 30 min occlusion of left anterior descending coronary artery followed by 120 min reperfusion.0.1％ dimethyl sulfoxide (the vehicle for diazoxide and wortmannin)/diazoxide at 0.47 mg· kg-1 · min-1/wortmannin at 1 μg·kg-1 ·min-1 was infused for 15 min starting from 25 min of ischemia in groups I/R,D and W respectively.In group DW wortmannin was infused at 5 min before diazoxide infusion.Blood samples were collected from left ventricle at the end of 120 min reperfusion for measurement of lactate dehydrogenase (LDH) activity.Myocardial infarct size was measured.Myocardial specimens were obtained for determination of apoptosis index (the number of apoptotic cells/the total number of cells examined) and expression of Bcl-2 and Bax.Bcl-2/Bax ratio was calculated.Results Diazoxide postconditioning significantly decreased plasma LDH activity,myocardial infarct size,apoptosis index and Bax expression in myocardium and increased myocardial Bcl-2 expression and Bcl-2/Bax ratio in group D compared with group I/R.Wortmannin partly counteracted the protective effects of diazoxide postconditioning against myocardial infarct.There was no significant difference in the above variables between groups I/R and W.Conclusion PI3K-Akt signal pathway is involved in the protective effects of diazoxide postconditioning on myocardium against I/R injury.