和胃理气方对肝胃不和型功能性消化不良大鼠VIP与CGRP水平及相关受体影响研究

Effects of Hewei Liqi Decoction on VIP and CGRP Levels and Related Receptors in Rats with Functional Dyspepsia of Liver and Stomach Disharmony

目的探讨和胃理气方对肝胃不和型功能性消化不良大鼠肠黏膜组织中血管活性肠肽(vasoactive intestinal peptide,VIP)与降钙素基因相关肽(calcitonin gene-related peptide,CGRP)的表达水平及相关受体的影响,阐明该方治疗肝胃不和型功能性消化不良的作用机理。方法对40只健康Wistar SPF级大鼠采取SPSS22.0软件平均分成4组,每组10只,分别为空白对照组、模型对照组、和胃理气方中药干预组和多潘立酮阳性药对照组。观察试验后大鼠胃肠动力变化,采用胃排空试验和小肠推进试验来测定胃排空率和小肠推进率;采用western-blot法及RT-PCR检测大鼠肠黏膜组织VIP及相关受体的表达。结果与多潘立酮阳性对照组大鼠及模型组大鼠相比较,中药组、西药组大鼠小肠推进率明显高于模型组,胃内残留率明显低于模型组,差异均有统计学意义(P<0.05);模型组大鼠肠黏膜组织中VIP及其受体血管活性肠肽1受体(vasoactive intestinal peptide receptor1,VPAC1)蛋白、CGRP及其受体活性修饰蛋白质1(receptor activity modifying protein1,RAMP1)蛋白的表达水平明显高于空白对照组,差异有统计学意义(P<0.05);中药组、西药组大鼠肠黏膜组织中VIP及其受体VPAC1蛋白、CGRP及其受体RAMP1蛋白表达水平明显低于模型组,差异有统计学意义(P<0.05);模型组大鼠肠黏膜组织中VIP mRNA、CGRP及其受体RAMP1 mRNA的表达水平与空白组比较,明显高于空白组,差异有统计学意义(P<0.05);中药组、西药组大鼠肠黏膜组织中VIP mRNA、CGRP及其受体RAMP1 mRNA的表达水平与模型组比较,明显降低,差异有统计学意义(P<0.05)。结论和胃理气方可能通过降低模型大鼠的VIP、CGRP以及相应受体的表达来治疗功能性消化不良。

Objective To investigate the effect of Hewei Liqi Decoction on the expression levels of VIP and CGRP and related receptors in rats with liver-stomach disharmony functional dyspepsia,and to elucidate the mechanism of this prescription in the treatment of liver-stomach disharmony functional dyspepsia. Methods 40 healthy Wistar SPF rats were divided into 4 groups by SPSS22.0 software,10 rats in each group,including blank control group,model control group,Hewei Liqi Decoction Chinese medicine intervention group and doperidone positive control group. Gastric emptying test and small intestine propulsion test were used to measure the gastric emptying rate and small intestine propulsion rate. The expressions of VIP and related receptors in rat intestinal mucosa were detected by Western-blot and RTPCR. Results Compared with rats in the domperidone positive control group and the model group,the small intestine propulsion rate of rats in the traditional Chinese medicine group and Western medicine group was significantly higher than that in the model group,and the gastric residual rate was significantly lower than that in the model group,showing statistical differences(P<0.05). The expression levels of ovarian division and proliferation pathway PCNA mRNA in both the high-dose and low-dose groups were significantly higher than those in the model group and the Western medicine control group(P<0.05). The expression levels of VIP and its receptor VPAC1 protein,CGRP and its receptor RAMP1 protein in the intestinal mucosal tissues of rats in the model group were significantly higher than those in the blank control group(P<0.05). The expression levels of VIP and its receptor VPAC1 protein,CGRP and its receptor RAMP1 protein in the rat intestinal mucosa of the traditional Chinese medicine group and the Western medicine group were significantly lower than that of the model group(P<0.05). The expression levels of VIP mRNA,CGRP and its receptor RAMP1 mRNA in the intestinal mucosal tissues of rats in the model group were significantly higher than those in the blank group,and the differences were statistically significant(P<0.05). The expression levels of VIP mRNA,CGRP and its receptor RAMP1 mRNA in the intestinal mucosa of rats in the traditional Chinese medicine group and the western medicine group were significantly lower than those in the model group(P<0.05). Conclusion Hewei Liqi Decoction may be used to treat functional dyspepsia by reducing the expression of VIP,CGRP and corresponding receptors in model rats.