异丙酚对大鼠肠缺血再灌注时肠粘膜细胞凋亡的影响

Effects of propofol on apoptosis in intestinal mucosa cells induced by intestinal ischemia/reperfusion in rats

目的评价异丙酚对大鼠肠缺血再灌注（I／R）时肠粘膜细胞凋亡的影响。方法24只SD大鼠随机分为3组（n=8），假手术组（S组）仅分离肠系膜上动脉（SMA）；肠缺血再灌注组（I／R组）阻断SMA1h；异丙酚组（P组）阻断SMA前30min腹腔注射异丙酚100mg／kg。于再灌注3h处死大鼠，取回肠末端组织，电镜及TUNEL法观察肠粘膜上皮细胞凋亡情况，并计算肠粘膜上皮细胞凋亡指数；测定肠粘膜超氧化物歧化酶（SOD）活性、丙二醛（MDA）及神经酰胺（CER）含量，RT-PCR法测定肠粘膜鞘磷脂酶（SMase）mRNA表达。结果与S组比较，I／R组肠粘膜SOD活性降低，MDA含量、CER含量、肠粘膜上皮细胞凋亡指数及SMasemRNA表达升高（P〈0．05或0．01）；与I／R组比较，P组MDA含量、CER含量、肠粘膜上皮细胞凋亡指数及SMasemRNA表达降低，S01）活性升高（P〈0．05或O．01）。I／R组肠粘膜SOD活性与CER含量呈负相关（r＝-0．775，P〈0．01），肠粘膜上皮细胞凋亡指数与CER含量呈正相关（r=0．852，P〈0．01）；P组肠粘膜上皮细胞凋亡指数与CER含量呈正相关（r=0．782，P〈0．01）。结论异丙酚可抑制大鼠肠缺血再灌注时肠粘膜上皮细胞凋亡，可能与清除氧自由基、下调SMasemRNA表达、减少CER生成有关。

Objective To investigate the effects of propofol on apoptosis in intestinal mucosa cells induced by intestinal ischemia/reperfusion （I/R） in rats and the mechanism. Methods Twenty-four SD rats of both sexes weighing 275-300 g were randomly divided into 3 equal groups （ n = 8 each） ： Ⅰ sham operation group; Ⅱ I/R group in which intestinal I/R was produced by clamping superior mesenteric artery for 1 h followed by 3 h reperfusion and m propofol group received propofol 100 mg/kg intraperitoneally 30 min before intestinal I/R. The animals were sacrificed by decapitation at the end of 3 h reperfusion. A small strip of small intestine was obtained from the distal end of ileum for （1） determination of apoptosis in intestinal mucosal epithelial cells （TUNEL） ; （2） determination of SOD activity, MDA and ceramide content and sphingo myelinase （SMase） mRNA expression in the intestinal mucous membrane and examination of uhrastructure with electron microscope. Apoptosis index was calculated. Results The SOD activity was significantly lower while the MDA and ceramide content, SMase mRNA expression and the apoptotic index were significantly higher in I/R group than in sham operation group. The SOD activity was significantly higher while MDA and ceramide content, SMase mRNA expression and apoptotic index were significantly lower in propofol group than in I/R group （ P 〈 0.05 or 0.01 ）. The ceramide content was positively correlated to apoptotic index （ r = 0.852, P 〈 0.01 ） and negatively correlated to SOD activity （ r = -0.775, P 〈 0.01 ） in I/R group. The ceramide content was positively correlated to the apoptotic index in propofol group （ r = 0.782, P 〈 0.01 ）. Conclusion Propofol can suppress apoptosis in the epithelial ceils of intestinal mucous membrane induced by intestinal I/R by removal of oxygen free redicals, down-regulation of SMase mRNA expression and suppression of ceramide production.