Dissertation
Dissertation > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology > Chinese medicine Experimental Pharmacology

Study on Regulating Intestinal Motion Function of Perilla Frutescens in Gastrointestinal Motility Dysfunction Rats

Author LiuRong
Tutor TangFang
School Tianjin Medical University
Course Traditional Chinese Medicine
Keywords colonic motility gastrointestinal motility dysfunction Perilla frutescens Ca2+ signal transduction membrane potential Ca2+-ATPase activity membrane fluidity
CLC R285.5
Type PhD thesis
Year 2007
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Objective:The gastrointestinal motility function is one of the most significant physiologicalfunctions of the digestive system. The normal gastrointestinal motion not onlytransmits chyme, but also promotes excreting the bacteria and its outcome in theintestinal tract. It also has the function of nonspecific immunity defense on thegastrointestinal tract. It is well known that under the stress conditions of trauma,operation, radiation, chemotherapy and severe infection, the symptoms ofgastrointestinal motion dysfunction will occur. The clinical symptoms includeabdominal distention, abdominal pain, nausea and vomiting, and so on. It is highlyimportant that the remedy should be used early for recovering gastrointestinalfunction, in order to come back to health and prevent complication. At present, it isdiscovered in study that there are many factors, which result in dysfunction ofgastrointestinal motility. The Western medicine for promoting gastrointestinalmotility have not better effect on it, while traditional Chinese medicine havesatisfying curative effect. So there are broad foregrounds of application of traditionalChinese medicine.It is full of volatile oil in the fragrant drugs, which can regulate the movement ofqi, eliminate the wetness-evil, remove distention and fullness, and invigorate thespleen and the stomach. The research of pharmacology and the effect of medicineprove that the volatile oil and aqueous components of the fragrant drugs both canexcite olfaction, gustation and gastric mucosa, increase gastric mucosa blood flow,promote the level of gastrin in plasma, strengthen gastric mucosa to resist the injuryof free radical, protect the function of the intestinal barrier in stress. They are alsoeffective to excite peristalsis of the intestinal tract and accelerate propulsion of thestomach and intestine. They suggest that the fragrant drugs have the function ofgastrointestinal movement regulation.Being one of the commonly used drugs in“fangxiang yunpi”therapy, Perillafrutescens have the effect on activating the function of spleen with fragrant scent,adjusting the middle jiao and invigorating the stomach. Both Caulis Perillae andFolium Perillae contain 0.3%-0.7% of volatile oil, whose main active ingredientsincludes perilladyhade, limonene, perillaketone, etc. Perilla frutescens has obviouscurative effect in clinic without sufficient scientific evidence, about restoring thefunction of the spleen, regulating qi movement of the middle jiao, and improving thecontaining, transporting and transforming function of the spleen and stomach. Thepurpose of the study is to explore the Perilla frutescens on adjusting gastrointestinalmotion function and demonstrating the fragrant drugs’“yunpi”mechanism. Lowerlimb ischemic-reperfusion (LIR) model was induced to simulate the dysfunction ofcolonic motility due to stress in wistar rats. To elucidate the promoting coloncontractile movement mechanism of Perilla frutescens, the average contractile amplitude of colonic muscle strips, the contraction response, cytoplasmic freecalcium concentration ([Ca2+]i), cell membrane potential, Ca2+-ATPase activity, cellmembrane fluidity of the colonic smooth muscle cells are examined.Methods:1 The gastrointestinal motion dysfunction model is induced in LIR rats.2 The isolated circular muscle strips and single smooth muscle cells of colon areinduced in rats. Through testing the changes of the average contractile amplitude ofcolonic smooth muscle strips and the average length of the colonic smooth musclecells, we explore the action and mechanism of Perilla frutescens in increasing coloniccontractile movement.3After stained with Flou3/AM and DiBAC4(3), the calcium concentration and thecell membrane potential in colonic smooth muscle cells were detected with laserscanning confocal microscope. The Ca2+-ATPase activity was determined withquantitative determination of phosphorus. It was discussed that the action andapproaches of Perilla frutescens regulating the [Ca2+]i.4 The membrane fluidity of colonic smooth muscle cells were examined, inorder to investigate the protecting cell membrane action of Perilla frutescens.Results:1 The dysfunction of colonic motion under stress was induced triumphantly byLIR model. After LIR rats were induced, the amplitude and tension of colonic musclestrips decreased markedly (P<0.05, P<0.001), and the average length of colonicsmooth muscle cells increased (P<0.05). Of LIR model, the calcium concentration ofthe colonic smooth muscle cells decreased, Ca2+-ATPase activity was increased, andcell membrane fluidity was reduced.2 Both water solution of Caulis Perillae and volatile oil of Folium Perillaeincreased the amplitude of LIR rats colonic muscle strips. The contraction effectcaused by two components of Perilla frutescens was inhibited by verapamil, not byatropine. But propanolol only inhibited the contraction due to water solutioncomponent.3 Both water solution of Caulis Perillae and volatile oil of Folium Perillaeincreased contraction of LIR rats colonic smooth muscle cells. The contraction causedby two components of Perilla frutescens was inhibited by EGTA or verapamil.4 Both water solution of Caulis Perillae and volatile oil of Folium Perillaeincreased [Ca2+]i of colonic smooth muscle cells in LIR rats. Not only IP(3)R blockerHeparin but also RyR blocker Ruthenium Red reduced the water solutioncomponent-evoked [Ca2+]i increase, but not the volatile oil component-evoked[Ca2+]i increase.5 Both water solution of Caulis Perillae and volatile oil of Folium Perillaedecreased membrane potential and Ca2+-ATPase activity of colonic smooth musclecells in LIR rats (P<0.05,P=0.001).6 Two components of Perilla frutescens all increased the membrane fluidity ofLIR rats colonic smooth muscle cells markedly (P<0.001). Conclusion:LIR model rats can induce the colonic motility disturbance under stress.Through increasing the amplitude of colonic muscle strips, contraction rate ofcolonic smooth muscle cells, and [Ca2+]i, water solution of Caulis Perillae andvolatile oil of Folium Perillae promote colonic contractive motion. Two componentsof Perilla frutescens promote cell membrane depolarization and open the L-typecalcium channel, so as to increase ca2+ influx. Ca2+-ATPase activity can be inhibitedby the two components too. The adjusting action of water solution of Caulis Perillaeis mediated by adrenalβreceptor. It increases [Ca2+]i in the process ofⅡCR andCICR, and regulates colonic dysfunction through IP3-Ca2+ signal transductionpathway. Two components of Perilla frutescens can maintain the membrane fluidityof colonic smooth muscle cells in LIR rats. The results show that Perilla frutescenshas the regulation effect on colonic contractive motion.

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