大麻素受体-2对小鼠结肠炎作用机制研究

目的：观察大麻素受体-2( CB2)对急性实验性小鼠结肠炎的作用,探讨CB2对肠黏膜内质网应激( ERS)影响。方法32只SPF小鼠随机分为正常组、模型组、CB2激动剂组、CB2拮抗剂组,每组8只。记录小鼠疾病活动度及结肠组织病理学评分,ELISA法检测结肠组织中炎症因子肿瘤坏死因子-α(TNF-α)、白介素-10(IL-10)水平,免疫组化法检测结肠组织CB2及ERS相关蛋白GRP78、CHOP表达,RT-PCR法检测结肠组织中GRP78、CHOP mRNA水平。结果与正常组比较,模型组TNF-α水平显著上调、IL-10水平下降( P<0．05),GRP78、CHOP蛋白及mRNA显著增高(P<0．05)。与模型组比较, CB2激动剂组 CB2表达明显增多( P <0．05),TNF-α水平下降(P <0．05),IL-10水平增多(P <0．05),GRP78、CHOP 蛋白及 mRNA 显著下降(P <0．05)。CB2拮抗剂组TNF-α、IL-10、ERS标记物水平与模型组差异无统计学意义。结论实验性结肠炎小鼠肠黏膜存在剧烈的ERS,CB2激动剂激活CB2表达后缓解结肠炎小鼠肠道炎症,可能与CB2抑制肠黏膜ERS有关。

Research the mechanism of cannabinoid receptor-2 on colitis in mice

Objective To observe the role of cannabinoid receptor-2 (CB2) in acute experimental colitis in mice, and to explore its effect on the endoplasmic reticulum stress ( ERS ) in the intestinal mucosa . Methods 32 SPF mice were randomly divided into normal group,model group,CB2 agonist group and CB2 antagonist group. Disease activity index( DAI) and colon histopathological score( HS) were evaluatd. The levels of TNF-α and IL-10 in colon tissue were detected by ELISA. The expression of CB2 and ERS markers GRP78, CHOP in colon tissues were de-tected by immunohistochemical. The mRNA levels of GRP78 and CHOP were detected by RT-PCR. Results Com-pared with the normal group,the level of TNF-αwas significantly higher and the level of IL-10 was significantly low-er(P<0. 05) in the model group,the expressions of GRP78, CHOP and its mRNA were significantly higher(P<0. 05). Compared with the model group,the expression of CB2 in the CB2 agonist group was significantly higher(P<0. 05),the level of TNF-α dropped and the level of IL-10 increased(P<0. 05),and the expressions of GRP78, CHOP and its mRNA were significantly reduced(P<0. 05). The level of IL-10,TNF-α and ERS markers had no significant difference bewteen CB2 antagonist group and the model group ( P>0. 05 ) . Conclusion Severe endo-plasmic reticulum stress exists in intestinal mucosa of experimental colitis mice. The CB2 agonist activates CB2 ex-pression,reducing colitis in mice. Its mechanism may be related to inhibiting ERS in intestinal mucosa.