VIP通过VPAC1/AKT通路抑制溃疡性结肠炎的肠道炎症反应

VIP inhibits the intestinal inflammation in ulcerative colitis through VPAC1/AKT signaling pathway

目的研究血管活性肠肽(VIP)以及VPAC1/AKT信号通路在溃疡性结肠炎(UC)中的作用。方法收集UC患者的结肠黏膜组织,检测VIP及其受体VPAC1的水平。实验小鼠分为3组:急性UC组小鼠饮用3%葡聚糖硫酸钠(DSS)7天诱导急性溃疡性结肠炎,VIP处理组小鼠在饮用3%DSS的第1、3、5日给予VIP腹腔注射(1 nmol/只),正常对照组小鼠自由饮蒸馏水。观察和记录小鼠的疾病活动指数。收集小鼠的结肠黏膜组织,检测VIP及VPAC1的水平、上皮细胞凋亡和增殖情况、AKT蛋白表达量,观察这些指标在VIP处理后的变化。结果急性UC患者和小鼠结肠黏膜的VIP和VPAC1水平均明显下调。予VIP处理后,小鼠UC疾病活动指数有所下降,结肠黏膜上皮细胞凋亡情况明显改善,增殖信号增多。VPAC1和p-AKT蛋白在小鼠急性UC结肠黏膜表达降低,给予VIP后均明显上调。结论 VIP通过VPAC1/AKT信号通路抑制UC的肠道炎症反应,抑制上皮细胞凋亡、促进上皮细胞增殖。

Objective To investigate the role of vasoactive intestinal peptide（ VIP） and VPAC1/AKT signaling pathway in ulcerative colitis（ UC）. Methods The colon mucosal tissues were collected from the UC patients and the expression of VIP and its receptor VPAC1 were detected. All mice were divided to three groups. In the acute UC group,mouse models with acute UC were established by exposure to 3% dextran sulfate sodium（ DSS） for 7 days. In the VIP group,each mouse was intraperitoneally injected with 1 nmol VIP on day 1,3,5 following 3% DSS administration. In the control group,the mice were allowed to drink distilled water. The disease activity index was recorded. The colon mucosal tissues were collected from the UC patients and mice. The changes in the expression of VIP and VPAC1,intestinal epithelial apoptosis and proliferation,the expression of AKT protein were observed and compared before and after VIP treatment. Results The expression of VIP and VPAC1 at mRNA and protein levels were significantly down-regulated in the colon mucosal tissues of patients and mice with acute UC. After VIP administration,the disease activity index was moderately decreased,the apoptosis of the epithelial cells of colon mucosal tissues was significantly mitigated and the proliferation of the epithelial cells of colon mucosal tissues enhanced in the DSS-induced UC mice. The expression levels of VPAC1 and p-AKT proteins in the colon mucosa from DSS-induced UC mouse models were down-regulated,which were significantly up-regulated after VIP treatment. Conclusions VIP can suppress the intestinal inflammatory response,inhibit the epithelial apoptosis and promote the epithelial proliferation through VPAC1/AKT signaling pathway in DSS-induced mouse models with acute UC.