白藜芦醇通过抑制铁死亡减轻肠缺血再灌注损伤的机制研究  

Mechanism of resveratrol alleviating intestinal ischemia reperfusion injury by inhibiting ferroptosis

作　　者：许宏森 贺俭[1] 赵伟成 XU Hongsen;HE Jian;ZHAO Weicheng(Department of Anesthesiology,Foshan Municipal First People’s Hospital,Foshan,Guangdong 528000,China;Department of Research and Teaching,Foshan Municipal Hospital of Traditional Chinese Medicine,Foshan,Guangdong 528000,China)

机构地区：[1]佛山市第一人民医院麻醉科,广东佛山528000 [2]佛山市中医院科教科,广东佛山528000

出　　处：《重庆医学》2025年第1期37-42,共6页Chongqing Medical Journal

基　　金：广东省中医药局面上项目(20222212);佛山市自筹经费类科技创新项目(2320001007565)。

摘　　要：目的观察白藜芦醇对肠缺血再灌注(IIR)损伤的作用及与铁死亡的相关性。方法构建小鼠IIR损伤模型,采用随机数字表法将小鼠分为假手术组(S组)、IIR损伤组(D组)、IIR损伤+白藜芦醇组(R组)、IIR损伤+铁死亡诱导剂组(F组)、IIR损伤+白藜芦醇+铁死亡诱导剂组(R+F组),各组采用不同的药物剂量及方法。取小肠组织切片行苏木精-伊红(HE)染色并在光镜下观察病理改变情况,使用ELISA测定丙二醛(MDA)、亚铁离子(Fe^(2+))、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平,Western blot检测谷胱甘肽过氧化物酶4(GPX4)和长链酯酰辅酶A合成酶4(ACSL4)蛋白表达。结果与S组比较,D组、R组、F组及R+F组小鼠小肠组织损伤加重,Chiu’s评分、MDA、Fe^(2+)水平升高,GSH和SOD水平降低(P<0.05),ACSL4蛋白表达上调,GPX4蛋白表达下调,差异有统计学意义(P<0.05)。与D组比较,R组小鼠小肠组织出现绒毛顶端下皮损伤,Chiu’s评分、MDA和Fe^(2+)水平降低,GSH和SOD水平升高,ACSL4蛋白表达下调,GPX4蛋白表达上调,差异有统计学意义(P<0.05);F组小鼠小肠组织出现绒毛脱落伴出血和溃疡形成,Chiu’s评分、MDA、Fe^(2+)水平升高,GSH和SOD水平降低,ACSL4蛋白表达上调,GPX4蛋白表达下调,差异有统计学意义(P<0.05)。与R组比较,R+F组小鼠小肠组织出现大量绒毛及固有膜破坏、脱落,Chiu’s评分、MDA水平、Fe^(2+)水平升高,GSH和SOD水平降低,ACSL4蛋白表达上调,GPX4蛋白表达下调,差异有统计学意义(P<0.05)。结论白藜芦醇可能通过抗氧化作用及抑制铁死亡减轻IIR引起的损伤。Objective To observe the effect of resveratrol on intestinal ischemia reperfusion(IIR)injury and its correlation with ferroptosis.Methods The mice IIR injury model was constructed.The mice were divided into the sham operation group(group S),IIR injury group(group D),IIR injury+resveratrol group(group R),IIR injury+ferroptosis inducer group(group F),IIR injury treatment+resveratrol+ferroptosis inducer group(group R+F).The various groups adopted different drug doses and methods.The intestinal tissue sections were taken for performing the HE staining and the pathological changes were observed by the light microscope.ELISA was used to detect the levels of malondialdehyde(MDA),ferrous ion(Fe^(2+)),glutathione(GSH)and super oxide dismutase(SOD).Western blot was used to detect the expression levels of glutathione peroxidase 4(GPX4)and acyl-coasynthetasling-chain family member 4(ACSL4)protein.Results Compared with the group S,the small intestine tissue damage in the group D,R,F and R+F was aggravated,the Chiu’s score,MDA and Fe^(2+)levels were increased,GSH and SOD levels were decreased(P<0.05),the ACSL4 protein expression was up-regulated,GPX4 protein expression was down-regulated,and the differences were statistically significant(P<0.05).Compared with the group D,the small intestine tissue in the group R appeared subapical villous injury,Chiu’s score,MDA and Fe^(2+)levels were decreased,the GSH and SOD levels were increased,the ACSL4 protein expression was down-regulated and GPX4 protein expression was up-regulated,and the differences were statistically significant(P<0.05);the small intestine tissue in the group F appeared villi fall off accompanied by bleeding and ulcer formation,Chiu’s score,MDA level and Fe^(2+)level were increased,GSH and SOD levels were decreased,ACSL4 protein expression level was up-regulated,GPX4 protein expression was down-regulated,and the differences were statistically significant(P<0.05).Compared with the R group,the small intestine tissue in the R+F group appeared a large number of vi

关 键 词：小肠 缺血再灌注损伤 铁死亡 白藜芦醇 

分 类 号：R614.1[医药卫生—麻醉学]