广藿香-陈皮挥发油对功能性消化不良大鼠的作用机制研究  

Study on the mechanism of patchouli-citrus volatile oil on functional dyspepsia rats

作　　者：沈长虹 孙晨[1] 姚子晴 程芳 程泽芳 刘波[1] 张若琪[1] Shen Changhong;Sun Chen;Yao Ziqing;Cheng Fang;Cheng Zefang;Liu Bo;Zhang Ruoqi(Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137)

机构地区：[1]成都中医药大学西南中药资源国家重点实验室,成都611137

出　　处：《中国抗生素杂志》2024年第12期1431-1440,I0001,共11页Chinese Journal of Antibiotics

基　　金：四川省科技计划资助项目(No.2022NSFSC1349);成都中医药大学杏林学者计划(No.QJRC2022023)。

摘　　要：目的研究广藿香-陈皮挥发油(patchouli-citrus volatile oil,PCO)是否可以通过调节胃窦肌张力、脑肠肽和自噬,增强胃动力和减轻不适感方面起到治疗功能性消化不良(functional dyspepsia,FD)大鼠的作用。方法将SD大鼠随机分为空白组(Control)、模型组(FD)、莫沙必利组(Mosapride)、广藿香-陈皮挥发油低剂量组(PCOL,100 mg/kg)和广藿香-陈皮挥发油高剂量组(PCOH,400 mg/kg)。给药7 d后,测定各组大鼠体质量、胃排空率(gastric emptying rate,GER)和肠推进率(intestinal propulsion rate,IPR);通过体外肌张力仪器检测胃窦环形肌张力的变化,评估PCO对大鼠肌张力的作用;苏木精-伊红染色(hematoxylineosin staining,HE)观察各组大鼠胃窦组织病理学改变;免疫组化检测各组大鼠胃窦组织酪氨酸激酶受体(c-kit)的表达;酶联免疫吸附测定法(enzyme linked immunosorbent assay,ELISA)检测大鼠血清中脑肠肽胃动素(motilin,MTL)、胃泌素(gastrin,GAS)、生长激素释放肽(ghrelin)、血管活性肠肽(vasoactive intestinal polypeptide,VIP)、5-羟基色胺(5-hydroxytryptamine,5-HT)的含量;定量聚合酶链式反应(quantitative real time polymerase chain reaction,qPCR)检测胃窦降钙素基因相关肽(calcitonin gene-related peptide,CGRP)mRNA的表达,蛋白免疫印迹法(western blot)检测胃窦组织中自噬相关蛋白苄氯素1(beclin1)、微管相关蛋白1轻链3(LC3)、p62的表达;结果PCO给药后可作用于胃窦上的乙酰胆碱受体、肾上腺素受体和5-HT受体,调节胃窦肌张力;还可以调节自噬相关p62、Beclin1和LC3的表达水平抑制ICC过度自噬以及调节FD大鼠脑肠肽(brain-gut peptides,BGP):提高MTL、GAS、Ghrelin水平,降低VIP、5-HT水平和胃窦CGRP mRNA表达,增强胃动力,促进消化功能以及减轻内脏超敏反应引起的疼痛。结论PCO可通过调节胃窦肌张力、抑制自噬以及调节血清脑肠肽水平,起到增强胃动力和调节脑肠轴方面起到治疗FD的作用。Objective To confirm the therapeutic effects of patchouli oil in combination with citrus oil(PCO)on functional dyspepsia(FD)in rats and explore its mechanism of action to enhance gastric motility and alleviate discomfort in terms of its action receptors regulating the muscle tone of the gastric sinusoidal circular muscle,brain-gut peptides,and autophagy.Methods SD rats were randomly divided into the blank(control)group,the model(FD)group,the mosapride group(mosapride),the patchouli-citrus volatile oil low dose group(PCOL,100 mg/kg),and the patchouli-citrus volatile oil high dose group(PCOH,400 mg/kg).After seven days of administration,the body mass,gastric emptying rate(GER),and intestinal propulsion rate(IPR)of rats in each group were measured;the changes in the ring muscle tone of the gastric sinus were detected by the in vitro muscle tone apparatus to evaluate the effect of PCO on the muscle tone of rats;the histopathological changes of the gastric sinus of the rats in each group were observed by hematoxylin-eosin staining(HE);the expression of c-kit of the gastric sinus tissues of the rats in each group was detected by immunohistochemistry;and ELISA was performed to examine the expression of the gastric sinus tissues of the rats in each group.The serum levels of motilin(MTL),gastrin(GAS),ghrelin,vasoactive intestinal polypeptide(VIP),and 5-hydroxytryptamine(5-HT)were detected by ELISA;the mRNA expression of calcitonin gene-related peptide(CGRP)in gastric sinus was detected by qPCR;and the expression of autophagy-related proteins(Beclin1,LC3 and p62)in gastric sinus tissue was detected by Western blotting.Results PCO could regulate the tone of the gastric sinus muscle by acting on the acetylcholine receptor,adrenergic receptor,and 5-HT receptor.It could also regulate the expression levels of autophagy-related p62,Beclin1,and LC3 to inhibit ICC over-autophagy as well as regulate brain-gut peptides(BGP)in FD rats,which could increase the levels of MTL,GAS,and Ghrelin,reduce VIP,5-HT levels,and mRNA expression of

关 键 词：功能性消化不良 广藿香挥发油 陈皮挥发油 脑肠肽 自噬 胃窦平滑肌 

分 类 号：R9[医药卫生—药学]