丙泊酚對肺缺血再灌注損傷大鼠肺上皮細胞凋亡的影響

1、丙泊酚對肺缺血再灌注損傷大鼠肺上皮細胞凋亡的影響華中科技大學(xué)同濟醫(yī)學(xué)院附屬協(xié)和醫(yī)院詹美俊 張詩海 姚尚龍作者單位：430022 武漢 華中科技大學(xué)附屬協(xié)和醫(yī)院麻醉科 目的 探討丙泊酚對肺臟缺血再灌注大鼠肺上皮細胞凋亡的影響。方法 采用大鼠肺原位熱缺血模型, 缺血1h。 170只大鼠隨機分為缺血再灌注組 (I/R組,n70), 丙泊酚再灌注組 (P組，n70) 以及相同機械通氣時間的假手術(shù)組（S組，n30）。按照再灌注時間的不同，分別于缺血1h 、再灌注0.5h、1h、2h、4h時間點(或假手術(shù)組相應(yīng)時間點)測定各組動脈血氧分壓(Pa02)、支氣管肺泡灌洗液(BALF)中中性粒細胞( PMN)百

2、分比、蛋白濃度, 以及肺組織丙二醛（MDA）、超氧化物歧化酶（SOD）含量和肺濕干重比值(W/D)。采用原位末端脫氧核苷酸轉(zhuǎn)移酶（TdT）介導(dǎo)的dUTP缺口末端標(biāo)記（TUNEL）技術(shù)，測定肺缺血再灌注下(或假手術(shù)組相應(yīng)時間點)肺上皮細胞凋亡指數(shù)。結(jié)果 在缺血1h時間點(或假手術(shù)組相應(yīng)時間點)三組間各種指標(biāo)無顯著差異性(P>0.05)。再灌注后,與S組相比, 相同時間點的I/R組和P組PMN百分比、蛋白濃度、MDA含量及凋亡指數(shù)均有所升高且具有顯著差異性（P<0.05）；而Pa02 和SOD含量有所降低且具有顯著差異性（P<0.05）。再灌注后,與I/R組相比, 相同時間點的P

3、組PMN百分比、蛋白濃度、MDA含量及凋亡指數(shù)均有所降低且具有顯著差異性（P<0.05）。P組Pa02下降程度較I/R組小，但二者之間的差異并無統(tǒng)計學(xué)意義（P>0.05）; 而SOD含量在再灌注后較I/R組有所升高且在再灌注4h時具有顯著差異性(P<0.05) 。相關(guān)性分析顯示，無論I/R組還是P組其凋亡指數(shù)與W/D均呈高度正相關(guān)（P<0.01）。結(jié)論 丙泊酚對大鼠缺血再灌注肺損傷具有保護作用,可能與其減少缺血再灌注時氧自由基的產(chǎn)生,抑制再灌注損傷肺組織中中性粒細胞的聚集以及抑制肺上皮細胞凋亡有關(guān)。關(guān)鍵詞 缺血; 再灌注損傷; 肺; 凋亡; 丙泊酚Relationshi

4、p of propofol in attenuating lung injury after ischemia-reperfusion with apoptosis in ratsZhan Mei-jun Zhang Shi-hai Yao Shang-long (Department of Anaesthesiology, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, 430022 Wuhan , China)Objective To observe the rel

5、ationship 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 prop

6、ofol 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

7、 , 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

8、 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

9、）, 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

10、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 gro

11、up 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 fr