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胃泌素通过STAT3途径对大鼠离体心脏缺血再灌注损伤发挥保护作用

, PP. 896-901

Keywords: 胃泌素,缺血再灌注损伤,Langendorff系统,转录激活因子

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Abstract:

目的探讨胃泌素(gastrin,GS)对SD大鼠离体心脏缺血再灌注损伤的保护作用以及STAT3在其中所起的作用。方法选取SPF级雄性健康SD大鼠48只(体质量250~300g),采用随机数字表法将其分为4组(n=12,其中随机6只检测左心室功能、TTC染色及心肌酶谱,其余6只进行TUNEL及Westernblot检测):空白对照组(B组)、胃泌素预处理对照组(GS组)、缺血再灌注组(IR组)、胃泌素预处理缺血再灌注组(GIR组)。应用Langendorff装置进行离体心脏灌注。B组持续灌注Krebs-Henseleit(K-H)缓冲液130min,GS组在持续灌注过程中的10~30min时间段给予了胃泌素(10-9mol/L)预处理;IR组及GIR组在阻断全心灌注前灌注30min,阻断灌注40min后再灌注60min,其中GIR组在阻断前20min给予胃泌素(10-9mol)预处理。每组中随机6只于阻断灌注前即刻(T0),再灌注15(T1)、30min(T2)、45(T3)、60min(T4)时记录左心室舒张末压(LVEDP)、左室发展压(LVDP)、左心室最大上升速率(+dp/dtmax);于T0、T4时收集冠状窦流出液,测定乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)浓度;灌注结束后留取心脏标本进行氯化三苯基四氮唑法(TTC)染色观察心肌梗死面积;每组其余6只进行TUNEL染色法观察心肌细胞凋亡情况以及Westernblot检测STAT3及磷酸化STAT3(p-STAT3)蛋白表达水平。结果B组与GS组各项指标无统计学差异(P>0.05);与前两组相比,IR组与GIR组从T1~T4时间点LVEDP增加,LVDP及+dp/dtmax降低,心肌梗死面积增大,LDH与CK-MB释放增加,凋亡细胞增加,p-STAT3蛋白表达增加,差异均有统计学意义(P<0.05);与IR组比较,GIR组从T1时间点开始左心室功能各项指标均有显著恢复(P<0.05),心肌梗死面积减少,LDH和CK-MB释放降低,心肌凋亡细胞显著减少[(19.2±1.0)%vs(14.2±1.0)%,P<0.05],且?p-STAT3?蛋白表达显著增加[(1.14±0.10)vs(1.63±0.10),P<0.05]。结论胃泌素通过STAT3途径在SD大鼠离体心脏缺血再灌注损伤中发挥保护作用。

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