白藜芦醇下调线粒体DNA修复酶对重症急性胰腺炎大鼠胰腺腺泡细胞凋亡的影响  

Resveratrol induces mitochondrial DNA repair enzyme downregulation and promotes pancreatic acinar cell apoptosis in rats with severe acute pancreatitis

作　　者：侯伊玲[1] 薄海[2] 刘子泉[2] 夏时海[3] 

机构地区：[1]天津武警医学院附属医院心血管内科,天津市300162 [2]天津武警医学院生理学与病理生理学教研室,天津市30016 [3]天津武警医学院附属医院消化科,天津市300162

出　　处：《世界华人消化杂志》2009年第28期2892-2898,共7页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30772883~~

摘　　要：目的:观察白藜芦醇对重症急性胰腺炎(SAP)胰腺细胞凋亡的影响,探讨线粒体凋亡通路及线粒体DNA修复酶OGG1与SAP腺泡细胞凋亡的关系.方法:30只SD大鼠随机分为假手术组(Sham组,只行开腹术,n=10),SAP模型组(SAP组,胆管逆行性注射牛黄胆酸钠制备SAP模型,n=10),白藜芦醇治疗组(Res组,SAP模型制作成功后,注射白藜芦醇溶液,n=10).测定各组血清淀粉酶,caspase-3,-9活性,高压液相色谱法测定线粒体DNA8-氧鸟嘌呤(8-oxodG)含量,罗丹明123法测定线粒体膜电位,流式细胞法检测胰腺腺泡细胞凋亡,Westernblot法测定细胞色素C释放及线粒体OGG1蛋白表达,并对胰腺组织进行病理学评分.结果:Res组与SAP组比较,血清胰淀粉酶、线粒体膜电位、线粒体OGG1蛋白表达量及胰腺病理损害评分显著降低(4761.98±501.45vs7428.91±526.49,18.42±2.04vs22.01±2.93,73.97±6.49vs159.46±12.85,5.74±0.95vs12.95±1.54,均P<0.05).胰腺腺泡细胞凋亡指数、线粒体细胞色素C释放、线粒体DNA8-oxodG含量及caspase-3,-9的活性显著升高(19.63±2.07vs12.45±1.93,174.31±15.93vs100±0.00,0.0590±0.074vs0.0336±0.0061,2.37±0.35vs1.95±0.19,2.07±0.25vs1.62±0.15,均P<0.05).结论:白藜芦醇通过下调胰腺腺泡细胞线粒体DNA修复酶OGG1,增加SAP胰腺腺泡细胞凋亡以减轻胰腺组织病理损害,对SAP具有治疗意义.AIM：To investigate the relationship among pancreatic acinar cell apoptosis,mitochondrial apoptosis pathway and mitochondrial DNA repair enzyme in severe acute pancreatitis （SAP）.METHODS：Thirty Sprague-Dawley rats were randomly divided into sham operation group （n=10）,model control group （SAP rats induced by retrograde injection of sodium taurocholate,n=10）,and resveratrol treatment group （SAP rats injected with resveratrol,n=10）.Serum amylase and caspase-3 and-9 activity in pancreatic acinar cells were detected. The level of 8-oxo-deoxyguanosine （8-oxodG） in mitochondrial DNA （mtDNA） was measured by high-pressure liquid chromatography （HPLC）. Mitochondrial cross-membrane potential （△ψ） was measured by monitoring the fluorescence spectrum of rhodamine 123. Pancreatic acinar cell apoptosis was detected by flow cytometry. Cytochrome c release and mitochondrial 8-oxoguanine DNA glycosylase 1 （OGG1） protein expression were determined by Western blot. Pathological damage of pancreatic tissue was scored. RESULTS： Serum amylase level, mitochondrial cross-membrane potential, mitochondrial OGG1 protein expression level and pancreatic pathological score were lower in the resveratrol treatment group than in the model control group （4761.98 ± 501.45 vs 7428.91± 526.49, 18.42 ± 2.04 vs 22.01± 2.93, 73.97 ± 6.49 vs 159.46 ± 12.85, and 5.74 ± 0.95 vs 12.95 ± 1.54, respectively; all P 〈 0.05）. Pancreatic acinar cell apoptosis index, cytochrome c release, 8-oxodG level and caspase-3 and -9 activity were higher in the resveratrol treatment group than in the model control group （19.63 ± 2.07 vs 12.45 ± 1.93, 174.31 ±15.93 vs 100 ±0.00, 0.0590 ± 0.074 vs 0.0336 ± 0.0061, 2.37 ± 0.35 vs 1.95 ±0.19, and 2.07 ± 0.25 vs 1.62 ± 0.15, respectively; all P 〈 0.05）. CONCLUSION： Resveratrol can reduce pancreatic pathological damage in SAP rats possibly by downregulating mitochondrial OGG1 protein expression and inducing pancreatic acinar cell apoptosis.

关 键 词：白藜芦醇 重症急性胰腺炎 凋亡 8-氧鸟嘌呤DNA糖基化酶 线粒体 

分 类 号：R285.5[医药卫生—中药学]