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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

刘业成 齐志伟 徐军 李毅 朱华栋 于学忠 马遂

刘业成, 齐志伟, 徐军, 李毅, 朱华栋, 于学忠, 马遂. 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[J]. 协和医学杂志, 2013, 4(3): 248-254. doi: 10.3969/j.issn.1674-9081.2013.03.006
引用本文: 刘业成, 齐志伟, 徐军, 李毅, 朱华栋, 于学忠, 马遂. 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[J]. 协和医学杂志, 2013, 4(3): 248-254. doi: 10.3969/j.issn.1674-9081.2013.03.006
Ye-cheng LIU, Zhi-wei QI, Jun XU, Yi LI, Hua-dong ZHU, Xue-zhong YU, Sui MA. Role of Exogenous Corticotropin-releasing Hormone in Cerebral Infarction-related Gastrointestinal Barrier Dysfunction[J]. Medical Journal of Peking Union Medical College Hospital, 2013, 4(3): 248-254. doi: 10.3969/j.issn.1674-9081.2013.03.006
Citation: Ye-cheng LIU, Zhi-wei QI, Jun XU, Yi LI, Hua-dong ZHU, Xue-zhong YU, Sui MA. Role of Exogenous Corticotropin-releasing Hormone in Cerebral Infarction-related Gastrointestinal Barrier Dysfunction[J]. Medical Journal of Peking Union Medical College Hospital, 2013, 4(3): 248-254. doi: 10.3969/j.issn.1674-9081.2013.03.006

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

doi: 10.3969/j.issn.1674-9081.2013.03.006
详细信息
    通讯作者:

    于学忠 电话:010-69159155, E-mail:yxz@medmail.com.cn

  • 中图分类号: R459.9

Role of Exogenous Corticotropin-releasing Hormone in Cerebral Infarction-related Gastrointestinal Barrier Dysfunction

More Information
  • 摘要:   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24 h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24 h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24 h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。
  • 图  1  各组实验大鼠下丘脑组织中CRH蛋白相对含量比较

    CRH:促肾上腺皮质激素释放激素;与C组比较,* *P<0.01;与I组比较,P<0.05;与A组比较,P<0.05

    图  2  各组实验大鼠胃组织中CRH蛋白相对含量比较

    CRH:同图 1;与C组比较,* *P<0.01;与I组比较,††P<0.01;与A组比较,‡‡P<0.01

    图  3  各组实验大鼠空肠组织中CRH蛋白相对含量比较

    CRH:同图 1;与C组比较,* *P<0.01;与I组比较,††P<0.01;与A组比较,‡‡P<0.01

    图  4  各组实验大鼠结肠组织中CRH蛋白相对含量比较

    CRH:同图 1;与C组比较,*P<0.05,* *P<0.01;与I组比较,††P<0.01;与A组比较,P<0.05,‡‡P<0.01

    表  1  各组大鼠实验室指标及胃大体评分结果(x ±s, n=10)

    组别 24 h尿肾上腺素
    (ng)
    24 h尿去甲肾上腺素
    (ng)
    24 h尿皮质醇
    (ng)
    尿蔗糖排出率
    (%)
    胃Guth评分 血浆DAO活性
    (U/L)
    血浆D-乳酸
    (mg/L)
    C组 13.11±7.56 156.65±60.28 106.13±47.47†† 0.54±0.29†† 1.5±1.4††‡‡ 16.33±5.41†† 7.35±1.24
    I组 42.28±19.86*‡ 265.96±82.09*‡ 239.85±73.85**‡‡ 2.19±0.88**‡‡ 13.9±5.3**‡‡ 26.37±8.09**‡ 14.37±3.70*‡
    A组 17.93±6.25 160.50±34.88 127.90±47.17 0.82±0.36†† 4.7±2.8**†† 19.47±5.89 7.51±1.22
    H组 70.96±27.07**‡‡ 339.25±109.24*‡ 248.87±93.38**‡‡ 0.96±0.42†† 7.1±4.5**† 19.68±4.35 9.22±1.95
    DAO:二胺氧化酶;与C组比较,* P<0.05, * * P<0.01;与I组比较,P<0.05, ††P<0.01;与A组比较,P<0.05, ‡‡P<0.01
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  • 收稿日期:  2013-04-26
  • 刊出日期:  2013-07-30

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