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丙泊酚对肺缺血再灌注大鼠肺上皮细胞凋亡影响的实验研究

Relationship of Propofol in Attenuating Lung Injury after Reperfusion with Apoptosis in Rats

【作者】 詹美俊

【导师】 张诗海;

【作者基本信息】 华中科技大学 , 麻醉学, 2007, 硕士

【摘要】 目的探讨丙泊酚对肺脏缺血再灌注大鼠肺上皮细胞凋亡的影响。方法采用大鼠肺原位热缺血模型,缺血1h。170只大鼠随机分为缺血再灌注组(R组),丙泊酚再灌注组(P组)以及相同机械通气时间的假手术组(S组)。按照再灌注时间的不同,分别于缺血1h、再灌注0.5h、1h、2h、4h时间点(或假手术组相应时间点)测定各组动脉血氧分压(Pa02)、支气管肺泡灌洗液(BALF)中中性粒细胞( PMN)百分比、蛋白浓度,以及肺组织丙二醛(MDA)、超氧化物歧化酶(SOD)含量和肺湿干重比(W/D)。采用原位末端脱氧核苷酸转移酶(TdT)介导的dUTP缺口末端标记(TUNEL)技术,测定肺缺血再灌注下(或假手术组相应时间点)肺上皮细胞凋亡指数。结果在缺血1h时间点(或假手术组相应时间点)三组间各种指标无显著差异性(P>0.05)。再灌注后,与相同时点的S组相比,R组和P组的PMN百分比、蛋白浓度、MDA含量及凋亡指数均有所升高且具有显著差异性(P<0.05或P<0.01);而Pa02和SOD含量有所降低且具有显著差异性(P<0.05)。再灌注后,与相同时点的R组相比, P组的PMN百分比、蛋白浓度、MDA含量及凋亡指数均有所降低且具有显著差异性(P<0.05或P<0.01)。P组Pa02下降程度较R组小,但二者之间的差异并无统计学意义(P>0.05);而SOD含量在再灌注后较R组有所升高且在再灌注4h时具有显著差异性(P<0.05)。相关性分析显示,无论R组还是P组其凋亡指数与W/D均呈高度正相关(P<0.01)。结论丙泊酚对大鼠缺血再灌注肺损伤具有保护作用,可能与其减少缺血再灌注时氧自由基的产生,抑制再灌注损伤肺组织中中性粒细胞的聚集以及抑制肺上皮细胞凋亡有关。

【Abstract】 Objective To observe the relationship of propofol attenuating lung injury after reperfusion with apoptosis in rats. Methods The model of situ pulmonary hilum occlusion was applied and warm ischemia was undergone for 1 hour. 170 Sprague-Dawley rats were randomized into 3 groups: reperfusion group and reperfusion group with propofol infusion, as well as time-matched sham group. Neutrophil count percent, protein concentration in BALF and malondialdehyde (MDA), superoxide dismutase(SOD), Wet/Dry (W/D) ratio in lung tissue, arterial blood gas analysis were measured at the time of 1 hour after pulmonary ischemia and 0.5h,1h,2h , 4h after reperfusion (or at the same time in time-matched sham group),respectively. Apoptotic cells were stained by the terminal deoxynucleotidyl transferase-mediate dUTP nick-end labeling (TUNEL) and apoptosis index were determined. Results There were no significant differences in all parameters in these groups at the time of 1 hour after pulmonary ischemia. Compared with time-matched sham group, neutrophil count percent and protein concentration in BALF, MDA, W/D ratio and apoptosis index in lung tissue increased significantly in reperfusion group and propofol group(P<0.05 or P<0.01), and SOD in lung tissue and PaO2 decreased significantly(P<0.05). Compared with time-matched reperfusion group, neutrophil count percent and protein concentration in BALF, MDA, W/D ratio and apoptosis index in lung tissue decreased significantly in the group with propofol infusion(P<0.05 or P<0.01). There was no significant difference in PaO2 between the reperfusion group and the group with propofol infusion (P>0.05), but there was a tendency of improvement. Compared with time-matched reperfusion group, there was a tendency of increase in SOD in lung tissue in the reperfusion group with propofol infusion and it increased significantly at the time of 4 hours after reperfusion (P<0.05). Correlation analysis showed that apoptosis index of reperfusion group and propofol group were direct correlation with W/D ratio of corresponding group. Conclusion Propofol can attenuate ischemia-reperfusion lung injury. As inhibiting neutrophil activation and oxygen free radical, inhibiting apoptosis is another mechanism of propofol in attenuating lung injury after reperfusion.

【关键词】 缺血再灌注(I/R)肺损伤凋亡丙泊酚
【Key words】 I/Rlung injuryapoptosispropofol
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