协和医学杂志

2013, v.4(03) 248-254

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外源性促肾上腺皮质激素释放激素在脑梗死大鼠胃肠屏障破坏中的作用
Role of Exogenous Corticotropin-releasing Hormone in Cerebral Infarction-related Gastrointestinal Barrier Dysfunction

刘业成;齐志伟;徐军;李毅;朱华栋;于学忠;马遂;
LIU Ye-cheng,QI Zhi-wei,XU Jun,LI Yi,ZHU Hua-dong,YU Xue-zhong,MA Sui Department of Emergency,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100730,China

摘要(Abstract):

目的探讨外源性促肾上腺皮质激素释放激素(corticotropin-releasing hormone,CRH)在脑梗死胃肠屏障破坏中的作用。方法雄性Wistar大鼠40只,随机分为伪手术组(C组)、脑梗死组(I组)、脑梗死+脑室CRH拮抗剂组(A组)、脑梗死+腹腔CRH组(H组),每组10只。留尿检测24h尿肾上腺素、去甲肾上腺素、皮质醇含量及蔗糖排出率,造模后24h行血浆二胺氧化酶活性、D-乳酸浓度检测;行胃大体Guth评分,Western blot法检测下丘脑、胃、空肠、结肠CRH蛋白的表达。结果各组应激强度指标24h尿肾上腺素、去甲肾上腺素、皮质醇含量变化趋势一致:与C组比较,I组、H组上述指标均显著升高(P均<0.05);与I组比较,A组上述指标均显著下降(P均<0.05),H组有轻度升高趋势,但差异无统计学意义;与A组比较,H组上述指标均显著升高(P均<0.05)。各组尿蔗糖排出率、胃Guth评分、血浆二胺氧化酶活性、血浆D-乳酸及下丘脑、胃、空肠、结肠CRH含量变化趋势一致:与C组比较,I组上述指标均显著升高(P均<0.05);与I组比较,A组上述指标均显著下降(P均<0.05),H组上述指标亦显著下降(P均<0.05);A组和H组间上述指标差异无统计学意义。结论脑梗死时胃肠道通透性增加,黏膜屏障破坏;中枢使用CRH受体拮抗剂能缓解脑梗死相关的胃肠屏障破坏;外周给予CRH会抑制脑内和胃肠道局部CRH蛋白的表达,同样能缓解脑梗死相关的胃肠屏障破坏。
Objective To explore the role of exogenous corticotropin-releasing hormone ( CRH) in cerebral infarction-related gastrointestinal barrier dysfunction. Methods Forty male Wistar rats were randomly divided into pseudo-operation group ( group C) ,cerebral infarction group ( group I) ,cerebral infarction + intracerebroventricular CRH antagonist group ( group A) ,and cerebral infarction + intraperitoneal CRH group ( group H) ,10 rats for each group. Urine samples were collected to determine the levels of 24-hour urine epinephrine, norepinephrine,cortisol,and sucrose. Blood samples were taken 24 hours after establishment of the models to determine the activity of diamine oxidase ( DAO) and the concentration of D-lactic acid ( D-lac) . The stomach was taken to determine gastric Guth score,and the tissues of hypothalamus,stomach,jejunum and colon were all taken to determine tissue CRH protein expression using Western blot. Results The changes of urinary cortisol and catecholamine were nearly the same: these indicators in group I and group H were significantly higher than those in group C ( P < 0. 05) ; in group A were significantly lower than those in group I ( P < 0. 05) ,in group H were slightly higher than those in group I,but with no significant difference; in group H were significantly higher than those in group A ( P < 0. 05) . The changes of urine sucrose exertion,gastric Guth score,plasma DAO activity,plasma D-lac,as well as hypothalamus and gastrointestinal CRH protein content were nearly the same: these indicators in group I were significantly higher than those in group C ( P < 0. 05) ; in group A were significantly lower than those in group I ( P < 0. 05) ,in group H were also significantly lower than in group I ( P < 0. 05) ; however,there was no significant difference between group A and group H. Conclusions After cerebral infarction,gastrointestinal barrier function is damaged. Central use of CRH blocker can decrease cerebral infarction-related gastrointestinal barrier dysfunction. Peripheral use of exogenous CRH can decrease the expression of CRH protein in the brain and the gastrointestinal tract,and also can decrease cerebral infarction-related gastrointestinal barrier dysfunction.

关键词(KeyWords): 促肾上腺皮质激素释放激素;脑梗死;胃肠黏膜屏障;应激
corticotropin-releasing hormone; cerebral infarction; gastrointestinal barrier dysfunction; stress

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作者(Author): 刘业成;齐志伟;徐军;李毅;朱华栋;于学忠;马遂;
LIU Ye-cheng,QI Zhi-wei,XU Jun,LI Yi,ZHU Hua-dong,YU Xue-zhong,MA Sui Department of Emergency,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100730,China

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