摘要
目的:观察丙泊酚对小鼠胃缺血/再灌注(ischemia-reperfusion,I/R)后胃黏膜损伤程度及胃黏膜细胞增殖及凋亡的影响,探讨丙泊酚的胃保护作用及可能机制.方法:72只♂昆明小鼠随机分为4组:假手术组(sham,S组)、I/R组、脂肪乳组(fat emulsion,F组)、丙泊酚组(propofol,P组).通过夹闭小鼠腹腔动脉30min后松开动脉夹再灌注1h制作胃I/R模型.取胃观察大体形态变化、计算胃黏膜损伤指数,HE染色光镜下观察病理形态学变化,比色法测定丙二醛(malondialdehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)活性,免疫组织化学方法和原位DNA末端标记(TUNEL)染色法分别检测胃黏膜细胞增殖和凋亡的表达情况,蛋白免疫印迹法(Westernblotting)测定胃黏膜组织中Bcl-2、Bax蛋白的表达.结果:腹腔注射25mg/kg丙泊酚后胃黏膜损伤明显减轻,具体表现为胃黏膜及黏膜下层的充血、水肿及糜烂均有明显改善;与I/R组相比,P组细胞内MDA含量明显降低,SOD活性增强(P<0.01);与I/R组相比,丙泊酚可明显抑制胃黏膜细胞凋亡(33.9%±1.3%vs60.8%±6.9%)、促进细胞增殖(16.0%±1.8%vs6.4%±1.2%)、下调Bax(0.453±0.025vs0.268±0.023)及上调Bcl-2蛋白(0.513±0.014vs0.752±0.015)的表达(均P<0.01).结论:丙泊酚能促进小鼠胃I/R后胃黏膜细胞增殖、抑制细胞凋亡,对胃I/R损伤有保护作用,其可能机制与其清除氧自由基、抑制脂质过氧化有关.
AIM：To observe the changes in proliferation and apoptosis of gastric mucosal cells in gastric ischemia-reperfusion（I/R） injury,and to clarifywhether propofol has a gastric protection effect and the possible mechanisms involved.METHODS：Seventy-two Kunming mice were randomly divided into four groups：sham operation group,I/R injury group,fat emulsion group,and propofol group.Except the sham operation group,I/R injury was induced in other groups by clamping the celiac artery for 30 min and allowing reperfusion for 1 h.The mice were f inally sacrificed to observe morphological changes and investigate gastric mucosal damage index（GMDI）.The histological changes of the stomach were observed using light microscopy.The content of malondialdehyde（MDA） and activity of superoxide dismutase（SOD） in gastric mucosal cells were measured by colorimetry analysis.Immunohistochemistry and TdT-mediated d-UTPbiotin nick end-labeling（TUNEL） assay were used to observe PCNA expression and apoptosis in gastric mucosa,and the expression of Bax and Bcl-2 proteins was determined by Western blot.RESULTS：Severe mucosal lesions induced by gastric I/R were considerably reduced following administration of propofol（25 mg/kg）;mucosal and submucosal hyperemia,edema,and deep erosion were improved significantly.Compared to the I/R group,treatment with propofol signif icantly reduced gastric mucosal MDA content and cell apoptosis（33.9% ± 1.3% vs 60.8% ± 6.9%,P 〈 0.01）,enhanced SOD activity,promoted cell proliferation（16.0% ± 1.8% vs 6.4% ± 1.2%,P 〈 0.01）,and regulated Bax（0.453 ± 0.025 vs 0.268 ± 0.023,P 〈 0.01） and Bcl-2（0.513 ± 0.014 vs 0.752 ± 0.015,P 〈 0.01） protein expression.CONCLUSION：Propofol protects against gastric gastric I/R injury possibly by promoting gastric mucosal cell proliferation and inhibiting apoptosis.
出处
《世界华人消化杂志》
CAS
北大核心
2012年第17期1495-1501,共7页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.81171041
江苏省自然科学基金资助项目
No.BK2011197
江苏省麻醉学重点实验室开放课题基金资助项目
No.KJS1103
江苏省2011年度普通高校研究生科研创新计划基金资助项目
No.CX2211-0752
徐州市社会发展科技计划基金资助项目
No.xzzd1051
徐州医学院院长基金资助项目
No.09KJZ17
No.09KJZ33~~
