褐藻糖胶对大鼠肠缺血再灌注损伤的作用及潜在机制  

Effect of fucoidan on intestinal ischemia-reperfusion injury in rats

作　　者：刘雪环 胡沙沙 王程[1] 栾晓[1] 郭菲菲[1] 孙向荣[1] 徐珞[1] LIU Xue-huan;HU Sha-sha;WANG Cheng;LUAN Xiao;GUO Fei-fei;SUN Xiang-rong;XU Luo(Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, Qingdao 266021, China;Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266555, China)

机构地区：[1]青岛大学基础医学院生理与病理生理学系,山东青岛266021 [2]青岛大学附属医院病理科,山东青岛266555

出　　处：《中国病理生理杂志》2019年第7期1296-1301,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81470815; No.81270467; No.81300281);山东省优秀中青年科学家科研奖励基金资助项目(No.BS2014YY009; No.81500414);中国博士后科学基金资助项目(No.2018M632627; No.2018M630749)

摘　　要：目的:探讨褐藻糖胶(fucoidan)对大鼠肠缺血再灌注(I/R)损伤的作用及潜在机制。方法:30只成年雄性Wistar大鼠随机分为3组:假手术(sham)组,缺血再灌注(I/R)组和褐藻糖胶(Fucoidan+I/R)组。Fucoidan+I/R组大鼠在缺血再灌注前7 d开始每天腹腔内注射褐藻糖胶(160 mg/kg);sham组及I/R组大鼠每天腹腔内注射等量的生理盐水,连续7 d。Sham组大鼠仅进行剖腹及肠系膜上动脉分离,I/R组及Fucoidan+I/R组大鼠剖腹后均将肠系膜上动脉夹闭1 h,再灌注2 h,建立肠缺血再灌注模型。各组大鼠经腹主动脉采血,测定血清二胺氧化酶(DAO)、D-乳酸(D-LA)、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)和IL-1β的水平;采血后取回肠末端组织,常规HE染色,观察组织损伤情况,同时检测肠组织中丙二醛(MDA)和谷胱甘肽(GSH)含量以及超氧化物歧化酶(SOD)和髓过氧化物酶(MPO)活性,此外,采用Western blot法检测肠组织中Bax、cleaved caspase-3和Bcl-2的蛋白水平。结果:与sham组和Fucoidan+I/R组比较,I/R组大鼠血清DAO、D-LA、TNF-α、IL-6和IL-1β水平显著增高(P<0.05),肠组织Chiu’s病理评分、MDA含量、MPO活性及Bax和cleaved caspase-3蛋白水平也显著增加(P<0.05),但肠组织中GSH含量、SOD活性和Bcl-2蛋白水平显著降低(P<0.05)。结论:褐藻糖胶可减轻I/R引起的肠组织损伤,机制可能与抗氧化、抗炎和抗凋亡效应有关。AIM: To investigate the effect and potential mechanism of fucoidan on intestinal ischemia-reperfusion(I/R) injury in rats. METHODS: Adult male Wistar rats were randomly divided into 3 groups: sham group, I/R group and Fucoidan+I/R group. Fucoidan at 160 mg/kg was intraperitoneally injected in rats of Fucoidan+I/R group 7 d prior to operation, and the equal volume of saline was intraperitoneally injected in rats of sham group and I/R group. The rats in I/R group and Fucoidan+I/R group underwent superior mesenteric artery occlusion for 1 h and then reperfusion for 2 h. Following reperfusion, the histomorphological changes of the ileum were examined by HE staining. The levels of diamine oxidase(DAO), D-lactic acid(D-LA), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and IL-1β were detected in the blood samples, the levels of malondialdehyde(MDA) and glutathione(GSH), the activity of superoxide dismutase(SOD) and myeloperoxidase(MPO), and the protein levels of Bax, cleaved caspase-3 and Bcl-2 were analyzed in intestinal tissue samples. RESULTS: Compared with sham group and Fucoidan+I/R group, the serum levels of DAO, D-LA, TNF-α, IL-6 and IL-1β were significantly increased in I/R group(P<0.05), Chiu’s score of intestinal tissue, MDA content, MPO activity, the levels of Bax and cleaved caspase-3 protein in the intestinal tissues were also significantly increased(P<0.05), while the tissue GSH content, SOD activity, and Bcl-2 protein levels were significantly decreased(P<0.05). CONCLUSION: Fucoidan attenuates intestinal tissue damage caused by I/R, which may be related to anti-oxidation, anti-inflammatory and anti-apoptotic effects.

关 键 词：缺血再灌注损伤 褐藻糖胶 细胞凋亡 炎症 

分 类 号：R363[医药卫生—病理学] R656.1[医药卫生—基础医学]