摘要
目的观察异丙酚对离体大鼠心肌缺血/再灌注损伤的影响并探讨其作用机制。方法应用langendorff离体心脏灌注系统建立心肌缺血/再灌注损伤模型。40只SD大鼠随机分为正常对照组、缺血/再灌注模型(I/R)组、异丙酚15、30、60μmol/L组。除正常对照外,各组分别平衡灌注20min后,常温全心停灌25min,再灌注30min。Powerlab/8s仪记录各组平衡末、缺血前及再灌30min时心率(HR)、左室发展压(LVDP)、左室舒张末压(LVDEP)、左室压力变化速率(±dp/dtmax)、冠脉流量(CF)等心功能指标;测定冠脉流出液中乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)活性;差速离心法提取心肌线粒体,测定线粒体活力、膜肿胀度、锰超氧化物歧化酶(Mn-SOD)活性和丙二醛(MDA)含量;原位末端转移酶标记法(TUNEL)检测心肌细胞凋亡,免疫组化法测定天冬氨酸特异的半胱氨酸蛋白酶(caspase)-3和热休克蛋白70(HSP70)的表达。结果异丙酚30、60μmol/L能明显改善缺血/再灌注后的心脏机械功能,降低冠脉流出液中LDH、CK的活性(P<0.05);异丙酚在30、60μmol/L浓度情况下心肌线粒体活力有所恢复,膜肿胀度减轻,Mn-SOD活性升高,MDA生成明显减少(P<0.05),心肌HSP70表达增多,心肌细胞凋亡率和caspase-3阳性细胞数明显减少(P<0.05)。结论异丙酚明显减轻缺血/再灌注所致的心肌线粒体的过氧化损伤,上调HSP70的表达,抑制caspase-3表达和心肌细胞凋亡的发生,可能是其心肌保护作用机制之一。
Objective To investigate the protective effect of different dose of propofol on ischemia/ reperfusion （ I/R ） injury in isolated rat hearts and clarify the possible molecular mechanism. Methods The langendorff model of ischemia/reperfusion was used. Forty isolated perfused rat hearts were divided into control, I/R, propofol 15,30,60μmol/L groups. Hearts were suffered globally ischemic for 25 min and 30 min with reperfusion. The cardiac function indexs such as the left ventricular developed pressure （LVDP）, the left ventricular end diastolic pressure （ LVDEP）, heart rate （ HR）, coronary arterial flow （ CF） were recorded at the time of equilibrate, before ischemia, the end of reperfusion respectively. The lactate dehydrogenase （ LDH ）, creatine kinase （ CK ） activities in the flow were measured. The swelling and activity of mitochondria The activity of Manganese Superoxide Dismutase （ Mn - SOD） and content of malondialdehyde （ MDA ） in myocardium mitechondria were also determined. The incidence of cardiomyocyte of apoptosis was evaluated by the TdT -mediated dUTP nick end labeling （TUNEL） staining and the expression of caspase - 3, HSP70 was detected by immunohistochemistry. Results Administration of propofol at the concentrations 30 and 60 μmol/L markedly ameliorated the cardiac function in CF, LVDP and LVDEP（ P 〈0： 05）, distinctly reduced the activities of the LDH and CK in the flow（P 〈 0.05 ） and the mitochondrial swelling,the content of MDA in myocardium mitochondrial（ P 〈0.05 ）, and significantly enhanced the activity of myocardium mitochondrial, Mn - SOD（ P 〈0.05 ） compared with I/R group. The apoptotic index and the expression of caspase -3 in propofol 30,60 μmol/L group were markedly lower than those of I/R group. The expression of HSP＇/0 in propofol 30,60 Ixmol/L group was significantly enhanced compared with I/R group. Conclusion It could be concluded that propofol administrated during ischemi- a/reperfusion has cardioprotective effects on ischemia/reperfusion injury in the isolated rat heart. The effect is associated with diminishing oxidative stress, protecting mitochondria from peroxidative injury, upregulating the expression of HSP70, and inhibiting the incidence of cardiomyocyte apoptosis.
出处
《中国急救医学》
CAS
CSCD
北大核心
2007年第3期236-239,共4页
Chinese Journal of Critical Care Medicine
基金
河北省卫生厅医学研究重点课题(No05036)
