CAJ | 학술논문

目的探讨心肌缺血再灌注致急性肺损伤(acute lung injury,ALI)机制及后处理保护效应. 方法选择雄性SD大鼠40只,按随机数字表法分为假手术组、心肌缺血/再灌注组(再灌注组)、缺血后处理组(后处理组)、缺血后处理+人第10号染色体缺失的磷酸酶及张力蛋白同源基因(phosphatase and tensin homolog deleted on chromosome ten,PTEN)抑制剂组(抑制剂组),每组10只.结扎左冠状动脉前降支制备心肌缺血/再灌注模型,后处理组于再灌注前1 min内,连续3个循环灌注10 s,缺血10 s,再灌注120 min后快速取肺.HE染色观察病理学变化;免疫组化法测定炎症因子、凋亡因子;TUNEL法测定细胞凋亡;Western blot检测蛋白激酶B(protein kinaseB,Akt)、磷酸化Akt(p-Akt)、糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)及磷酸化GSK-3β(p-GSK-3β). 结果与假手术组比较,其余三组的B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、IL-10表达减少,Bcl-2相关X蛋白(Bcl-2 associated X protein,Bax)、天冬氨酸蛋白水解酶-3(cysteinyl aspartate specific proteinase,Caspase-3)、IL-6、IL-8、TUNEL表达增多(P＜0.01);与再灌注组比较,后处理组、抑制剂组的Bax、Caspase-3、IL-6、IL-8、TUNEL表达减少,Bcl-2、IL-10表达增多(P＜0.01).Akt、p-Akt、GSK-3β水平四组比较差异无统计学意义,再灌注组p-GSK-3β较其余三组明显降低(P＜0.01). 结论在心肌缺血/再灌注损伤早期,信号通路尚未发挥作用时,炎症因子的激活直接引起p-GSK-3β降低,导致大鼠ALI,后处理可以部分减轻肺损伤.
목적 탐토심기결혈재관주치급성폐손상(acute lung injury,ALI)궤제급후처리보호효응. 방법 선택웅성SD대서40지,안수궤수자표법분위가수술조、심기결혈/재관주조(재관주조)、결혈후처리조(후처리조)、결혈후처리+인제10호염색체결실적린산매급장력단백동원기인(phosphatase and tensin homolog deleted on chromosome ten,PTEN)억제제조(억제제조),매조10지.결찰좌관상동맥전강지제비심기결혈/재관주모형,후처리조우재관주전1 min내,련속3개순배관주10 s,결혈10 s,재관주120 min후쾌속취폐.HE염색관찰병이학변화;면역조화법측정염증인자、조망인자;TUNEL법측정세포조망;Western blot검측단백격매B(protein kinaseB,Akt)、린산화Akt(p-Akt)、당원합성매격매-3β(glycogen synthase kinase-3β,GSK-3β)급린산화GSK-3β(p-GSK-3β). 결과 여가수술조비교,기여삼조적B림파세포류-2(B-cell lymphoma-2,Bcl-2)、IL-10표체감소,Bcl-2상관X단백(Bcl-2 associated X protein,Bax)、천동안산단백수해매-3(cysteinyl aspartate specific proteinase,Caspase-3)、IL-6、IL-8、TUNEL표체증다(P＜0.01);여재관주조비교,후처리조、억제제조적Bax、Caspase-3、IL-6、IL-8、TUNEL표체감소,Bcl-2、IL-10표체증다(P＜0.01).Akt、p-Akt、GSK-3β수평사조비교차이무통계학의의,재관주조p-GSK-3β교기여삼조명현강저(P＜0.01). 결론 재심기결혈/재관주손상조기,신호통로상미발휘작용시,염증인자적격활직접인기p-GSK-3β강저,도치대서ALI,후처리가이부분감경폐손상.
Objective To investigate the mechanism of myocardial ischemia and reperfusion-induced acute lung injury (ALl) and protective effect of ischemic postconditioning.Methods Forty SD rats were allocated to sham group,myocardial ischemia/reperfusion group (reperfusion group),ischemic postconditioning group (postconditioning group),and ischemic postconditioning + phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibiting group (inhibitor group) according to the random number table,with 10 rats per group.Myocardial ischemia/reperfusion was induced by left anterior descending coronary artery occlusion.Postconditioning was performed within 1 minute before reperfusion consisting of 3 10 s cycles of reperfusion followed by 10 s occlusion.Lung was immediately removed 120 minutes after reperfusion for HE stain,immunohistochemical detection of inflammatory factors and apoptosis factors,TUNEL assay of cell apoptosis,and Western blot of protein kinase B (Akt),phospho-Akt (p-Akt),glycogen synthase kinase-3β (GSK-3β),and phospho-GSK-3β (p-GSK-3β).Results Down-regulated B-cell lymphoma-2 (Bcl-2) and IL-10 and up-regulated Bcl-2 associated X protein (Bax),cysteinyl aspartate specific proteinase-3 (Caspase-3),IL-6 as well as IL-8 were observed in other 3 groups compared with sham group (P ＜0.01).Moreover,down-regulated Bax,Caspase-3,IL-6,IL-8 as well as TUNEL and up-regulated Bcl-2 as well as IL-10 were observed in reperfusion group compared to postconditioning group and tensor group (P ＜ 0.01).No statistical differences were found among the four groups in levels of Akt,p-Akt,and GSK-3β,but level of p-GSK-3β was significantly down-regulated in reperfusion group compared to other 3 groups(P ＜ 0.01).Conclusion Development of ALI may relate to down-regulation of p-GSK-3β evoked directly by the release of inflammation factors in early period of myocardial ischemia/reperfusion and ischemic postconditioning may attenuate the condition.