全反式维甲酸预处理对肝血流阻断大鼠肠道的保护作用  

Protective effect of all-trans retinoic acid pretreatment against rat intestinal injury induced by hepatic inflow occlusion

作　　者：王钟兴[1] 黄婵燕[1] 方佳峰[2] 陈图锋[2] 

机构地区：[1]中山大学附属第一医院麻醉科,广东广州510080 [2]中山大学附属第三医院胃肠外科,广东广州510630

出　　处：《中国病理生理杂志》2013年第9期1620-1624,共5页Chinese Journal of Pathophysiology

基　　金：广东省科技计划(No.2010B060900030;No.2010B031600206)

摘　　要：目的:探讨全反式维甲酸(ATRA)对肝血流阻断所致肠道损伤的影响和机制。方法:32只雄性SD大鼠,随机分为4组:假手术(sham)组、肝血流阻断(HIO)组、溶媒对照(DMSO+HIO)组和ATRA预处理(ATRA+HIO)组。ATRA预处理组以ATRA 15 mg·kg-1·d-1灌胃,溶媒对照组以等体积二甲基亚砜(DMSO)灌胃,共10 d。Pringle’s法建立肝血流阻断模型,持续30 min,解除阻断再灌注2 h后,采集各组大鼠末端回肠和血清。光镜下观察回肠病理改变、行肠黏膜组织Chiu氏评分;比色法检测血清二胺氧化酶(DAO)水平、回肠组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性;ELISA法测定血清白细胞介素(IL)-1β及肿瘤坏死因子(TNF)-α水平;Western blotting检测组织中胞浆锰超氧化物歧化酶(MnSOD)和胞核NF-κB p65蛋白的表达量。结果:相对于HIO组和DMSO+HIO组,ATRA能缓解肝血流阻断后肠黏膜组织病理损伤,降低Chiu氏评分和血清DAO水平(P<0.05),减少回肠组织中MDA含量(P<0.05),提高SOD活性(P<0.05),增加组织MnSOD的表达(P<0.05),减少胞核NF-κB p65蛋白含量(P<0.05),降低血清IL-1β和TNF-α水平(P<0.05)。结论:ATRA通过增加组织抗氧化能力,抑制NF-κB通路的激活,减少促炎因子的产生,从而减轻大鼠肝血流阻断造成的肠道损伤。AIM：To investigate the effect of all-trans retinoic acid （ATRA） on the intestinal injury induced by hepatic inflow occlusion （HIO） and its mechanisms. METHODS：Thirty-two male Sprague-Dawley rats were randomly divided into four groups： sham group, HIO group, dimethyl sulfoxide （DMSO） ＋ HIO group and ATRA （15 mg·kg-1·d-1） ＋ HIO group. The hepatoduodenal ligament of the rats in the latter three groups was occluded （Pringle manoeuvre） by clamp for 30 min. After reperfusion for 2 h by release of the clamp, samples of distal ileum and serum were collected. Histological changes and Chiu’s scores of the ileac mucosa were evaluated under light microscope. Serum content of diamine oxidase （DAO）, and ileac tissue levels of malonaldehyde （MDA） and superoxide dismutase （SOD） were analyzed by colorimetry. Serum concentrations of interleukin （IL）-1β and tumor necrosis factor （TNF）-α were evaluated by enzyme-linked immunosorbent assay method. Expression of manganese superoxide dismutase （MnSOD） in cytoplasm and nuclear factor kappa B （NF-κB） p65 in nucleus was assessed by Western blotting. RESULTS：Compared with sham group and DMSO＋HIO group, ATRA significantly reduced the mucosal Chiu’s scores, the serum content of DAO and the tissue level of MDA, enhanced the serum activity of SOD and the protein expression of MnSOD, and decreased the content of NF-κB p65 in nucleus （all P〈0.05）. Subsequently, ATRA significantly reduced the levels of TNF-α and IL-1β in serum （P〈0.05）. CONCLUSION：ATRA can attenuate rat intestinal injury induced by HIO through improving the antioxidant capacity of tissue, inhibiting the activation of NF-κB and suppressing the overexpression of pro-inflammatory factors.

关 键 词：全反式维甲酸 肝血流阻断 再灌注损伤 肠 

分 类 号：R656.7[医药卫生—外科学]