Endogenous cannabinoid system regulates intestinal barrier function in vivo through cannabinoid type 1 receptor activation.
Endogenous cannabinoid system regulates intestinal barrier function in vivo through cannabinoid type 1 receptor activation.
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内源性大麻素系统通过大麻素1型受体激活调节体内肠道屏障功能。
DOI：
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
J. Leza
中科院分区：
文献类型：
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作者：
S. Zoppi;J. Madrigal;B. Perez;I. Marín;J. Caso;L. Alou;B. García;A. Colón;J. Manzanares;M. Gómez;L. Menchén;J. Leza
应激对胃肠道的有害影响似乎主要是通过诱导肠屏障功能障碍和随后的细微粘膜炎症介导的。大麻素1受体（Cannabinoid 1 receptor, CB1R）在哺乳动物肠道中有生理表达。本研究的目的是研究应激暴露后CB1R在维持粘膜稳态中的可能作用。将CB1R基因敲除小鼠（CB1R(-/-)）及其野生型小鼠（WT）连续4天，每天暴露于固定和声学（IA）应激下2小时。对诱导型一氧化氮合酶和环氧化酶（NOS2和COX2）的结肠蛋白表达、IgA的产生、对（51）Cr-EDTA的通透性以及细菌向肠系膜淋巴结的易位进行了评估。应激暴露诱导CB1R（-/-）小鼠结肠黏膜促炎酶NOS2和COX2的表达高于WT动物。这些变化与CB1R（-/-）动物更大程度的结肠屏障功能障碍有关，这是由以下因素决定的：1)在基础条件下和IA应激暴露后，IgA分泌显著降低，2)细胞旁对（51）Cr-EDTA的渗透性增加，以及3)细菌易位增加。在CB1R（-/-）小鼠中，利莫那班的药理拮抗作用再现了应激诱导的结肠促炎酶的增加。综上所述，体内CB1R通过调节肠道IgA分泌和细胞旁通透性对结肠起到保护作用。胃肠道内大麻素系统的药理学调节可能在暴露于压力后发生肠道炎症和屏障功能障碍的条件下治疗有用。
The deleterious effects of stress on the gastrointestinal tract seem to be mainly mediated by the induction of intestinal barrier dysfunction and subsequent subtle mucosal inflammation. Cannabinoid 1 receptor (CB1R) is expressed in the mammalian gut under physiological circumstances. The aim of this investigation is to study the possible role of CB1R in the maintenance of mucosal homeostasis after stress exposure. CB1R knockout mice (CB1R(-/-)) and their wild-type (WT) counterparts were exposed to immobilization and acoustic (IA) stress for 2 h per day during 4 consecutive days. Colonic protein expression of the inducible forms of the nitric oxide synthase and cyclooxygenase (NOS2 and COX2), IgA production, permeability to (51)Cr-EDTA, and bacterial translocation to mesenteric lymph nodes were evaluated. Stress exposure induced greater expression of proinflammatory enzymes NOS2 and COX2 in colonic mucosa of CB1R(-/-) mice when compared with WT animals. These changes were related with a greater degree of colonic barrier dysfunction in CB1R(-/-) animals determined by 1) a significantly lower IgA secretion, 2) higher paracellular permeability to (51)Cr-EDTA, and 3) higher bacterial translocation, both under basal conditions and after IA stress exposure. Pharmacological antagonism with rimonabant reproduced stress-induced increase of proinflammatory enzymes in the colon described in CB1R(-/-) mice. In conclusion, CB1R exerts a protective role in the colon in vivo through the regulation of intestinal secretion of IgA and paracellular permeability. Pharmacological modulation of cannabinoid system within the gastrointestinal tract might be therapeutically useful in conditions on which intestinal inflammation and barrier dysfunction takes place after exposure to stress.
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影响因子：
14.2
作者：
Groschwitz, Katherine R.;Hogan, Simon P.
通讯作者：
Hogan, Simon P.
影响因子：
15.9
作者：
MADARA, JL;STAFFORD, J
通讯作者：
STAFFORD, J
δ 9-四氢大麻酚对诱导型一氧化氮合酶基因表达的减弱是通过抑制核因子-κ B/Rel 激活来介导的。
DOI：
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发表时间：
1996
期刊：
Molecular pharmacology.
影响因子：
--
作者：
Jeon,YJ;Yang,KH;Pulaski,JT;Kaminski,NE
通讯作者：
Kaminski,NE
DOI：
10.1152/ajpgi.00162.2004
发表时间：
2004-11-01
影响因子：
4.5
作者：
Ogawa, H;Iimura, M;Kagnoff, MF
通讯作者：
Kagnoff, MF
DOI：
10.1152/ajpgi.1994.267.5.g794
发表时间：
1994-11-01
影响因子：
4.5
作者：
SAUNDERS, PR;KOSECKA, U;PERDUE, MH
通讯作者：
PERDUE, MH