良附丸治疗胃寒型功能性消化不良的药效学研究

Pharmacodynamic Study of Liangfu Pill in the Treatment of Functional Dyspepsia of Stomach-cold Type

目的探讨良附丸治疗胃寒型功能性消化不良(FD)的药效学及作用机制。方法采用小鼠胃肠排空实验考察良附丸对胃肠运动的影响;采用小鼠醋酸扭体法、甲醛致痛法考察良附丸的镇痛作用。SPF级大鼠72只,随机分为正常对照组,模型对照组,良附丸小、中、大剂量组,莫沙必利组,除正常对照组其余均构建胃寒型FD大鼠模型,造模结束后,各组给予相应药物治疗7 d。记录大鼠的一般情况,进行糖水偏好实验、旷场实验和胃肠运动实验;采用酶联免疫吸附测定实验(ELISA)检测5-羟色胺(5-HT)、胃动素(MTL)、血管活性肠肽(VIP)、P物质(SP)的含量,透射电镜观察胃窦、结肠组织中嗜铬细胞,免疫组化(IHC)法观察胃窦及空肠组织中5-HT的表达。结果与正常对照组比较,良附丸组小鼠疼痛显著缓解,胃排空率及小肠推进率升高;在胃寒型FD大鼠中,与模型对照组比较,良附丸组的一般情况明显好转,进食量、饮水量呈明显上升趋势,糖水偏好百分率和旷场实验得分均显著增高,MTL和SP的含量均显著上升,VIP显著下降,胃肠组织中的嗜铬细胞增多,5-HT阳性表达显著增加。结论良附丸对FD具有潜在的治疗作用,其作用机制可能与调控脑肠肽尤其是5-HT水平有关。

Objective To investigate the pharmacodynamics and mechanism of action of Liangfu pill in the treatment of functional dyspepsia(FD)of stomach-cold type.Methods The effect of Liangfu pill on gastrointestinal motility was studied by gastrointestinal emptying test in mice.The analgesic effect of Liangfu pill was investigated by acetic acid writhing test and formaldehyde-induced pain test in mice.A total of 72 SPF rats were randomly divided into normal control group,model control group,low-,medium-and high-dose group of Liangfu pill,and mosapride group.Despite of the normal control group,all the rats were constructed with FD model of stomach cold.After the end of modeling,the drugs was given to each group for 7 days.The general conditions of the rats were recorded,two-bottle choice test and the open field test were performed,the gastrointestinal emptying test was performed,the contents of serotonin(5-HT),motilin(MTL),vasoactive intestinal peptide(VIP),substance P(SP)were measured by ELISA,the levels of chromaffin cells in the gastric antrum and colon tissues were observed by transmission electron microscopy,and the expression of 5-HT in the gastric antrum and jejunum tissues was observed by immunohistochemistry(IHC).Results Compared with the normal control group,the Liangfu pill group significantly relieved pain and promoted gastric emptying and small intestine propulsion in mice.Compared with the model control group,the general condition of the Liangfu pill group was significantly better,with a clear upward trend in food intake and water intake,a significant increase in the percentage of two-bottle choice test and the score for the open field test,a significant increase in the content of MTL and SP,a significant decrease in VIP,an increase in chromaffin cells in the gastrointestinal tissue,and a significant increase in the positive expression of 5-HT.Conclusion Liangfu pill has potential therapeutic effects on FD,and the mechanism may be related to the regulation of brain-gut peptide,especially 5-HT levels.