CAJ | 학술논문

目的研究磷脂酰肌醇-3-激酶/丝氨酸苏氨酸蛋白激酶/内皮型一氧化氮合酶(phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase,PI3K/Akt/eNOS)信号通路在二氮嚷后处理大鼠在体心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤中的作用. 方法 40只雄性SD大鼠完全随机分为5组,每组8只:假手术组(S组)、I/R组、二氮嗪组(D组)、PI3K抑制剂渥蔓菁霉素组(W组)和二氮嗪+渥蔓菁霉素组(DW组).结扎左冠状动脉前降支30 min、再开放120 min,建立在体心肌I/R损伤模型,S组不结扎.再灌注5 min前,5组依次分别经股静脉输入0.1％二甲基亚砜(dimethyl sulfoxide,DMSO)1 ml/kg、0.1％ DMSO 1 ml/kg、二氮嗪7 mg/kg、渥蔓菁霉素15 μg/kg,DW组于输入二氮嗪前5 min输入渥蔓菁霉素；所有药物均输注15 min.再灌注末,测定血浆心肌肌钙蛋白I(cardiac troponin I,cTnI)浓度,苏木精-伊红(HE)染色观察心肌病理变化,免疫组化分析eNOS的表达情况. 结果与S组比较,其余4组cTnI显著增高(P＜0.01),心肌明显损伤,eNOS表达增高(P＜0.05或P＜0.01).与I/R组比较,D组和DW组cTnI[(36.5±5.2) μg/L与(44.5±4.5)μg/L vs (64.7±11.1) μg/L]明显降低(P＜0.01),心肌病理改变减轻,eNOS表达增高[(0.515±0.136)％与(0.394±0.100)％ vs (0.241±0.077)％](P＜0.01).与D组比较,DW组cTnI明显增高[(44.5±4.5) μg/L vs (36.5±5.2) μg/L] (P＜0.05),心肌损伤加重,eNOS表达降低[(0.394±0.100)％ vs (0.515±0.136)％] (P＜0.01). 结论二氮嗪后处理减轻大鼠心肌I/损伤的作用部分与PI3K/Akt/eNOS信号通路激活有关.
목적 연구린지선기순-3-격매/사안산소안산단백격매/내피형일양화담합매(phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase,PI3K/Akt/eNOS)신호통로재이담양후처리대서재체심기결혈/재관주(ischemia/reperfusion,I/R)손상중적작용. 방법 40지웅성SD대서완전수궤분위5조,매조8지:가수술조(S조)、I/R조、이담진조(D조)、PI3K억제제악만정매소조(W조)화이담진+악만정매소조(DW조).결찰좌관상동맥전강지30 min、재개방120 min,건립재체심기I/R손상모형,S조불결찰.재관주5 min전,5조의차분별경고정맥수입0.1％이갑기아풍(dimethyl sulfoxide,DMSO)1 ml/kg、0.1％ DMSO 1 ml/kg、이담진7 mg/kg、악만정매소15 μg/kg,DW조우수입이담진전5 min수입악만정매소；소유약물균수주15 min.재관주말,측정혈장심기기개단백I(cardiac troponin I,cTnI)농도,소목정-이홍(HE)염색관찰심기병리변화,면역조화분석eNOS적표체정황. 결과 여S조비교,기여4조cTnI현저증고(P＜0.01),심기명현손상,eNOS표체증고(P＜0.05혹P＜0.01).여I/R조비교,D조화DW조cTnI[(36.5±5.2) μg/L여(44.5±4.5)μg/L vs (64.7±11.1) μg/L]명현강저(P＜0.01),심기병리개변감경,eNOS표체증고[(0.515±0.136)％여(0.394±0.100)％ vs (0.241±0.077)％](P＜0.01).여D조비교,DW조cTnI명현증고[(44.5±4.5) μg/L vs (36.5±5.2) μg/L] (P＜0.05),심기손상가중,eNOS표체강저[(0.394±0.100)％ vs (0.515±0.136)％] (P＜0.01). 결론 이담진후처리감경대서심기I/손상적작용부분여PI3K/Akt/eNOS신호통로격활유관.
Objective To study the role of phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in diazoxide-postconditioning against in vivo rat myocardial ischemia/reperfusion (I/R) injury.Methods Forty SD rats were randomly divided into five groups:sham operation group (S),I/R,diazoxide group (D),inhibitor of PI3K wortmannin group (W) and diazoxide + wortmannin group (DW).In vivo myocardial I/R injury model was made by ligation of left anterior descending coronary artery 30 min followed by 120 min reperfusion except for S group.Each group was infused respectively with 0.1％ dimethyl sulfoxide (DMSO),0.1％ DMSO,diazoxide 7 mg/kg,wortmannin 15 μg/kg and diazoxide via the femoral vein 5 min before reperfusion,and wortmannin was given 5 min before administration of diazoxide in DW group.All drugs were continuously infused for 15 min.At the end of reperfusion,the plasma concentration of cardiac troponin Ⅰ (cTnI) was measured; myocardial pathological changes were examined by HE staining; and the expression of eNOS was evaluated via immunohistochemisty.Results Compared with S group,concentration of cTnI was significantly decreased (P＜0.01),myocardium damaged obviously,and the expression of eNOS was markedly increased in other four groups.Compared with I/R group,concentration of cTnI was significantly decreased [(36.5±5.2) μg/L and (44.5±4.5) μg/L vs (64.7±11.1) μg/L](P＜0.01) and myocardial pathological changes were markedly slighter,accompanying with significant high expression of eNOS [(0.515±0.136)％