异功散对功能性消化不良大鼠胃肠动力和肠黏膜屏障功能的影响

Effects of Yigong Powder on gastrointestinal motility and intestinal mucosal barrier function in rats with functional dyspepsia

目的观察异功散对功能性消化不良(FD)大鼠胃肠动力和肠黏膜屏障功能的影响,探讨其可能作用机制。方法将60只雄性SD大鼠随机分为对照组、模型组、多潘立酮组、异功散低剂量组、异功散中剂量组和异功散高剂量组,每组10只。除对照组外,其余组大鼠采用不规则喂食夹尾刺激法建立FD模型。刺激14 d后,多潘立酮组给予多潘立酮3.5 mg/(kg·d)灌胃,异功散低、中、高剂量组分别给予3 g/(kg·d)、6 g/(kg·d)、12 g/(kg·d)的异功散灌胃,对照组和模型组给予生理盐水灌胃,均1次/d,持续14 d。观察各组大鼠的一般情况、体重增量和食物摄入量,检测胃排空率和小肠推进率,HE染色观察胃窦组织的病理形态,ELISA法检测血清胃动素(MTL)、胃泌素(GAS)、血管活性肠肽(VIP)和降钙素基因相关肽(CGRP)水平,Western blot法检测十二指肠组织中闭合蛋白(Occludin)、紧密连接蛋白1(ZO-1)、连接黏附分子1(JAM-1)表达情况。结果与对照组比较,模型组大鼠活动减少,毛发润泽度、反应力均较差,体重增量、食物摄入量、胃排空率、小肠推进率、血清MTL和GAS水平及十二指肠组织中Occludin、ZO-1、JAM-1蛋白相对表达量均明显降低(P均<0.05),血清VIP和CGRP水平均明显增高(P均<0.05);大鼠胃窦黏膜层可见大量炎性细胞浸润,胃黏膜变薄、破裂。与模型组比较,多潘立酮组和异功散中、高剂量组大鼠灌胃后活动、毛发润泽度、反应力均明显改善,体重增量、食物摄入量、胃排空率、小肠推进率、血清MTL和GAS水平及十二指肠组织中Occludin、ZO-1、JAM-1蛋白相对表达量均明显增高(P均<0.05),血清VIP和CGRP水平均明显降低(P均<0.05);胃窦黏膜层仅见少量炎性细胞浸润。结论异功散可能通过调节脑肠肽的分泌和紧密连接相关蛋白的表达来改善胃肠动力、保护肠黏膜屏障,从而对FD起到保护作用。

Objective It is to investigate the effects of Yigong Powder on the gastrointestinal motility and intestinal mucosal barrier function of rats with functional dyspepsia(FD),and to explore its possible mechanisms of action.Methods Sixty male SD rats were randomly divided into control group,model group,domperidone group,Yigong Powder low-dose group,Yigong Powder medium-dose group and Yigong Powder high-dose group,with 10 rats in each group.Except for the control group,the rats in the remaining groups were fed irregularly and stimulated with tail pinch to establish FD models.After 14 d of stimulation,the domperidone domperidone group was given domperidone 3.5 mg/(kg·d)by gavage,the low-dose,medium-dose and high-dose group of Yigong Powder were given Yigong Powder 3 g/(kg·d),6 g/(kg·d),and 12 g/(kg·d)by gavage,respectively,and the control group and model group were given normal saline by gavage,all once daily,continuously treated for 14 days.The general condition,body weight increase and food intake of rats in each group were observed,the gastric emptying rate and small intestinal propulsion rate were detected,the pathological morphology of gastric sinusoidal tissues was observed by HE staining,the levels of serum gastrin(MTL),gastrin(GAS),vasoactive intestinal peptide(VIP),and calcitonin gene-related peptide(CGRP)were detected by ELISA,and the expressions of occludin,zonula occludens-1(ZO-1),and junctional adhesion molecule 1(JAM-1)in duodenal tissues were detected by Western blot.Results Compared with the control group,the rats in the model group showed reduced activity,with bad hair moistening and responsiveness,the body weight increase,food intake,gastric emptying rate,small intestinal propulsion rate,levels of serum MTL and GAS,and the relative expressions of Occludin,ZO-1,and JAM-1 proteins in duodenal tissues were all significantly decreased(all P<0.05),and the levels of serum VIP and CGRP were significantly increased(all P<0.05);a large amount of inflammatory cell infiltration was seen in the mucosal layer of the gastric sinus of rats,and the gastric mucosa was thinned and ruptured.Compared with the model group,the activity,hair moistening,and responsiveness of rats in the domperidone group and the medium-dose and high-dose groups of Yigong Powder were significantly improved,and the body weight increase,food intake,gastric emptying rate,small intestinal propulsive rate,levels of serum MTL and GAS,and the relative expressions of Occludin,ZO-1,and JAM-1 proteins in duodenal tissues were all significantly increased(all P<0.05),and the levels of serum VIP and CGRP were significantly reduced(all P<0.05);only a small amount of inflammatory cell infiltration was seen in the mucosal layer of the gastric sinus.Conclusion Yigong Powder may protect FD by regulating the secretion of brain-gut peptides and expression of tight junction-related proteins to protect the intestinal barrier and improve gastrointestinal motility.