本文關(guān)鍵詞：基于胃腸動(dòng)力探討健脾方劑對(duì)FD脾虛證病證結(jié)合大鼠模型的作用研究　出處：《中國(guó)中醫(yī)科學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 功能性消化不良 香砂六君子 脾虛Ⅰ號(hào)方 胃腸激素 脾虛證 胃腸動(dòng)力

【摘要】：研究背景功能性消化不良(functional dyspepsia,FD)系一類臨床上常見和多發(fā)的胃腸功能紊亂性疾病,主要表現(xiàn)為餐后飽脹不適、早飽、上腹痛和上腹燒灼感等,根據(jù)羅馬ⅣV將其分為餐后不適綜合征(Postprandial Distress syndrome,PDS)和上腹痛綜合征(EpigastricPainSyndrome,EPS),其中餐后不適綜合征主要表現(xiàn)為早飽及餐后飽脹感,上腹痛綜合征主要為位于上腹部的疼痛或燒灼感。其在全球發(fā)病率可達(dá)11.5%～29.2%[1],影響了全球1/4以上的人口。其病理生理機(jī)制并不十分明確,目前西醫(yī)專家多認(rèn)為與胃腸動(dòng)力異常、內(nèi)臟敏感性增高、胃酸分泌過多、幽門螺桿菌感染、腦-腸軸、自主神經(jīng)系統(tǒng)和胃腸激素、社會(huì)心理學(xué)因素等相關(guān),主要通過促進(jìn)胃腸動(dòng)力、降低內(nèi)臟高敏感、治療HP感染、抑制胃酸分泌、保護(hù)胃黏膜及精神心理治療等,多采用單靶點(diǎn)對(duì)癥治療。中醫(yī)認(rèn)為功能性消化不良上腹燒灼感主要與“嘈雜”相對(duì)應(yīng),“上腹痛”與“胃痛”、“胃脘痛”對(duì)應(yīng),而餐后不適與早飽主要與“痞滿”相應(yīng),基本病機(jī)為脾胃升降失司,功能失調(diào),胃氣壅滯,以脾虛氣滯為主,治療以健脾理氣為主,中醫(yī)藥在FD的治療方面有其獨(dú)特的優(yōu)勢(shì),本研究通過采用健脾方劑通過在體及離體方式干預(yù)FD脾虛證病證結(jié)合大鼠模型,研究其作用機(jī)制。研究目的1.通過對(duì)脾虛Ⅰ號(hào)方及香砂六君子湯進(jìn)行在體藥效及藥理學(xué)實(shí)驗(yàn),觀察健脾方劑對(duì)FD脾虛證病證結(jié)合模型大鼠胃腸動(dòng)力的作用,探討其治療FD的可能作用機(jī)制;2.通過離體狀態(tài)下給予FD脾虛證病證結(jié)合模型大鼠不同劑量健脾方劑進(jìn)行干預(yù),探討健脾方劑對(duì)大鼠不同部位胃組織胃動(dòng)力的直接影響;3.觀察離體狀態(tài)下不同健脾組合物對(duì)不同部位胃組織胃動(dòng)力的直接影響。研究?jī)?nèi)容實(shí)驗(yàn)一、FD脾虛證病證結(jié)合大鼠模型的建立與評(píng)價(jià)目的:建立與評(píng)價(jià)FD脾虛證病證結(jié)合大鼠模型材料和方法:將30只雄性SD大鼠(乳鼠)隨機(jī)分為正常組、單純碘乙酰胺灌胃組(疾病組)、碘乙酰胺灌胃疊加小平臺(tái)站立組(病證結(jié)合組),出生7日購(gòu)進(jìn),3天適應(yīng)性飼養(yǎng)。出生10日SD雄性乳鼠,正常組每日以2%蔗糖溶液灌胃;模型組每日以0.1%碘乙酰胺溶液灌胃,每只0.2ml,連續(xù)灌胃6天;大鼠3周齡時(shí),剔除母鼠,分籠,至大鼠6周齡后,繼續(xù)給予正常鼠飼料喂養(yǎng);碘乙酰胺疊加小平臺(tái)站立組每日18:00-8:00進(jìn)行小平臺(tái)站立,連續(xù)14天。造模結(jié)束后分別觀察一般情況、體重、進(jìn)食量、飲水量、抓力、糖水偏好情況、血清乳酸、D-木糖、淀粉酶含量等。結(jié)果:(1)一般情況:病證結(jié)合模型組大鼠體重、進(jìn)食量、飲水量與正常組及疾病模型組相比,明顯偏低(P0.05)。(2)抓力測(cè)定:病證結(jié)合模型組大鼠抓力與正常組和疾病模型組相比顯著降低(P0.05)。(3)糖水偏好情況:病證結(jié)合模型組大鼠在糖水消耗量方面有所降低,但與正常組及疾病模型組相比,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(4)血清學(xué)指標(biāo):與正常組及疾病模型組比較,病證結(jié)合模型組血清D-木糖、淀粉酶含量顯著降低(P0.05),血清乳酸含量顯著增加(P0.01)。實(shí)驗(yàn)二、健脾方劑對(duì)FD脾虛證病證結(jié)合大鼠模型在體胃腸動(dòng)力作用機(jī)制的研究目的:觀察脾虛Ⅰ號(hào)方及香砂六君子湯對(duì)FD脾虛證模型大鼠胃腸動(dòng)力的作用,從胃排空、小腸推進(jìn)實(shí)驗(yàn)及血清胃腸激素水平探討其治療FD的可能作用機(jī)制。材料與方法:采取碘乙酰胺疊加小平臺(tái)站立法建立FD脾虛證病證結(jié)合大鼠模型,實(shí)驗(yàn)動(dòng)物隨機(jī)分為正常組、模型組、西藥組(多潘立酮組)、脾虛Ⅰ號(hào)方高劑量組、中劑量組、低劑量組、香砂六君子高劑量組、中劑量組、低劑量組。造模結(jié)束后,按每10ml·kg-1體重大鼠給藥1ml以脾虛Ⅰ號(hào)方或香砂六君子或多潘立酮或蒸餾水灌胃14d。在此過程中,定時(shí)觀察并記錄大鼠體重、進(jìn)食量、飲水量、抓力、毛色、活動(dòng)等一般情況。治療完成后,給予大鼠灌胃營(yíng)養(yǎng)性半固體糊,計(jì)算各組大鼠胃內(nèi)殘留率及小腸推進(jìn)比。麻醉狀態(tài)下腹主動(dòng)脈取血,用ELISA或比色法檢測(cè)血清中淀粉酶、D-木糖、乳酸、胃動(dòng)素(MTL)、胃泌素(GAS)、促胃生長(zhǎng)素(Ghrelin)、膽囊收縮素(CCK)、生長(zhǎng)抑素(SS)、血管活性腸肽(VIP)含量。結(jié)果:1 一般情況治療前,與正常組比較,模型組及其余各組大鼠體重、進(jìn)食量、飲水量、抓力均顯著降低(P0.05)。與模型組比較,除正常組外,其余各組間大鼠體重、進(jìn)食量、飲水量、抓力均無(wú)明顯差異(P9.05)。治療后,與模型組比較,西藥組,香砂低、中、高劑量組,脾虛中、高劑量組大鼠體重顯著升高(P0.05)。香砂高劑量組,脾虛高劑量組大鼠飲水量顯著升高(P0.05)。香砂高、中、低劑量組,脾虛高、中、低劑量組大鼠進(jìn)食量顯著升高(P0.05)。西藥組,香砂高、中劑量組,脾虛高、低劑量組大鼠抓力顯著升高(P0.05)。與西藥組比較,香砂高劑量組,脾虛高劑量組大鼠飲水量顯著升高(P0.05)。脾虛高、中劑量組大鼠進(jìn)食量顯著升高(p0.05)。各組大鼠體重、抓力與西藥組比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。2胃內(nèi)殘留率和小腸推進(jìn)比(1)與正常組比較,模型組大鼠胃內(nèi)殘留率顯著高于正常組(p0.01);與模型組比較,西藥組、脾虛低劑量、香砂高劑量組大鼠胃內(nèi)殘留率顯著降低(P0.05);與西藥組比較,脾虛中、高劑量組,香砂低、中劑量組大鼠胃內(nèi)殘留率顯著高于西藥組(P0.05)。(2)與正常組比較,模型組大鼠小腸推進(jìn)比顯著低于正常組(P0.05);與模型組比較,西藥組、脾虛低、中、高劑量組、香砂高劑量組小腸推進(jìn)比顯著劑量增加(P0.05);與西藥組比較,脾虛高劑量組小腸推進(jìn)比顯著高于西藥組(P0.01),香砂低劑量小腸推進(jìn)比顯著低于西藥組(P0.05)。3血清學(xué)指標(biāo)(1)與正常組比較,模型組血清D-木糖含量顯著低于正常組(P0.05);與模型組比較,西藥組、脾虛低劑量組血清D木糖含量均顯著高于模型組(P0.01);與西藥組比較,各中藥組血清D-木糖含量差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(2)與正常組比較,模型組血清淀粉酶含量顯著降低于(P0.05);與模型組比較,西藥組、脾虛中、高劑量組,香砂低、高劑量組血清淀粉酶含量均顯著高于模型組(P0.05);與西藥組比較,各中藥組血清淀粉酶含量差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(3)與正常組比較,模型組血清乳酸含量模型組顯著升高(P0.05);與模型組比較,給藥后西藥組、脾虛中、高劑量,香砂低、中劑量血清乳酸含量均顯著低于模型組(P0.05);與西藥組比較,各中藥組血清乳酸含量差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(4)與正常組比較,模型組血清胃動(dòng)素含量顯著低于正常組(p0.01);與模型組比較,西藥組、脾虛低、中、高劑量組,香砂低、中、高劑量組血清胃動(dòng)素含量均高于模型組(p0.01);與西藥組比較,脾虛中、高劑量組,香砂低、中劑量組血清胃動(dòng)素含量均高于西藥組(P0.05)。(5)與正常組比較,模型組血清胃泌素含量顯著低于正常組(P0.01);與模型組比較,西藥組、脾虛低、中、高劑量組,香砂低、中、高劑量組血清胃泌素含量均高于模型組(P0.01);與西藥組比較,脾虛高劑量組血清胃泌素含量顯著高于西藥組(P0.05)。(6)與正常組比較,模型組血清促胃生長(zhǎng)素含量顯著低于正常組(P0.05);與模型組比較,西藥組、脾虛中、高劑量組,香砂高劑量組血清促胃生長(zhǎng)素含量顯著高于模型組(p0.05);與西藥組比較,香砂高劑量組、脾虛高劑量組血清促胃生長(zhǎng)素含量顯著高于西藥組(P0.05)。(7)與正常組比較,模型組血清膽囊收縮素含量高于正常組,但差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);與模型組比較,香砂低劑量組血清膽囊收縮素含量顯著低于模型組(p0.05);與西藥組比較,香砂高劑量組血清膽囊收縮素含量顯著高于西藥組(P005)(8)與正常組比較,模型組血清血管活性腸肽含量顯著高于正常組(P0.05);與模型組比較,香砂高劑量組顯著高于模型組(P0.05);與西藥組比較,各中藥組血清血管活性腸肽含量差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)(9)與正常組比較,模型組血清生長(zhǎng)抑素含量顯著高于正常組(P0.05);與模型組比較,香砂中劑量組血清生長(zhǎng)抑素含量顯著降低(P0.05);與西藥組比較,各中藥組血清生長(zhǎng)抑素含量差異均無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)實(shí)驗(yàn)三、健脾方劑對(duì)FD脾虛證模型大鼠離體組織胃動(dòng)力的作用研究目的:通過觀察脾虛Ⅰ號(hào)方及香砂六君子湯干預(yù)功能性消化不良脾虛證模型大鼠離體胃組織,從胃體、胃竇收縮幅度和頻率及胃底張力角度,試圖明確脾虛Ⅰ號(hào)方及香砂六君子湯離體調(diào)節(jié)胃動(dòng)力的作用機(jī)制。材料與方法:采取碘乙酰胺疊加小平臺(tái)法建立功能性消化不良脾虛證大鼠模型,實(shí)驗(yàn)動(dòng)物分為正常組、模型組,造模后取正常組與模型組大鼠胃體、胃底、胃竇不同組織,比較模型組與正常組各部位收縮的差異,離體給予不同濃度的脾虛Ⅰ號(hào)方及香砂六君子湯,觀察藥物對(duì)模型胃體、胃竇收縮幅度和頻率及胃底張力的影響。結(jié)果:(1)在離體狀態(tài)下,模型大鼠的胃底張力顯著高于正常組,差異有統(tǒng)計(jì)學(xué)意義(P0.05),模型大鼠的胃竇、胃體收縮幅度和頻率均顯著低于正常組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。(2)給予不同濃度的脾虛Ⅰ號(hào)方后可見FD模型大鼠胃底張力隨濃度增加而增高,差異有統(tǒng)計(jì)學(xué)意義(p0.05),而香砂六君子的胃底張力隨給藥濃度而降低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。(3)給脾虛Ⅰ號(hào)方后胃竇收縮幅度隨給藥濃度而明顯增強(qiáng),差異有統(tǒng)計(jì)學(xué)意義(P0.05),其收縮頻率無(wú)明顯變化(P0.05),給予香砂六君子低濃度時(shí)可顯著提高胃竇收縮幅度及頻率(P0.05),當(dāng)濃度達(dá)到一定劑量時(shí)則抑制胃竇收縮頻率和幅度(P0.05)。(4)給脾虛1號(hào)方后胃體收縮幅度隨給藥濃度而減小,差異有統(tǒng)計(jì)學(xué)意義(P0.05),其收縮頻率則明顯增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05),給予香砂六君子不同濃度時(shí)胃體收縮幅度及頻率均明顯減小,差異有統(tǒng)計(jì)學(xué)意義(P0.05),當(dāng)濃度達(dá)到一定劑量時(shí)則抑制胃竇收縮頻率和幅度(P0.05)。實(shí)驗(yàn)四、不同健脾藥物組合對(duì)正常大鼠離體胃動(dòng)力的作用研究目的:通過觀察不同健脾藥對(duì)對(duì)離體大鼠胃竇收縮幅度及胃底張力的作用,探討離體狀態(tài)下不同健脾藥對(duì)對(duì)胃動(dòng)力的調(diào)節(jié)作用。材料與方法:將實(shí)驗(yàn)動(dòng)物分為四組,取大鼠胃竇、胃底不同組織,離體給予不同濃度的健脾藥、健脾理氣藥、健脾化濕藥、健脾溫中藥的藥物組合,觀察藥物對(duì)胃竇收縮幅度及胃底張力的作用差異。結(jié)果:(1)中藥健脾組、健脾化濕組、健脾溫中組可顯著提高胃底張力,差異有統(tǒng)計(jì)學(xué)意義(P0.05),健脾理氣組可顯著降低胃底張力,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。(2)中藥健脾組,健脾化濕組可增加胃竇收縮幅度,差異有統(tǒng)計(jì)學(xué)意義(P0.05),健脾理氣組可顯著減小胃竇收縮幅度,差異有統(tǒng)計(jì)學(xué)意義(P0.05),健脾溫中組對(duì)胃竇作用效果無(wú)差異(P0.05)。研究結(jié)論1.碘乙酰胺灌胃疊加改良小平臺(tái)法站立制作出的功能性消化不良動(dòng)物模型符合脾虛證特征,具有胃動(dòng)力障礙表現(xiàn)。2.健脾方劑可以改善FD大鼠胃腸道吸收功能及乳酸堆積造成的肢倦乏力狀態(tài)。3.健脾方劑方可直接促進(jìn)模型大鼠胃排空及小腸推進(jìn)或通過改善胃腸激素,調(diào)節(jié)胃腸運(yùn)動(dòng),其中脾虛Ⅰ號(hào)方的小腸推進(jìn)作用優(yōu)于香砂六君子。4.在離體狀態(tài)下,健脾方劑可直接作用于胃組織而改善胃動(dòng)力,健脾方劑及健脾藥對(duì)從不同角度發(fā)揮其對(duì)胃腸動(dòng)力的雙向調(diào)節(jié)作用,且呈現(xiàn)劑量依賴性。
[Abstract]:The research background of functional dyspepsia (functional dyspepsia FD) is a kind of clinical common and multiple gastrointestinal functional disorders, mainly for distention, postprandial satiety, upper abdominal pain and abdominal burning sensation, according to the Rome V IV will be divided into postprandial distress syndrome (Postprandial Distress syndrome, PDS) and epigastric pain syndrome (EpigastricPainSyndrome, EPS), the postprandial distress syndrome mainly for early satiety and postprandial fullness, epigastric pain syndrome is mainly located in the upper abdominal pain or burning sensation in the world. Its incidence rate is up to 11.5% ~ 29.2%[1], the impact of the global 1/4 of the population. Its pathophysiological mechanism is not very clear, the current Western experts believe that with abnormal gastrointestinal motility, visceral hypersensitivity, excessive secretion of gastric acid, Helicobacter pylori infection, brain gut axis, autonomic nervous system and gastrointestinal hormone, social psychology Other related factors, mainly by promoting gastrointestinal motility, reduce visceral sensitivity, the treatment of HP infection, inhibition of gastric acid secretion, protect the gastric mucosa and psychological treatment, the use of single target therapy. Chinese medicine functional dyspepsia epigastric burning sensation and "noisy" corresponding "pain" and "stomach", "stomachache" correspondence, and postprandial discomfort and early satiety and "fullness", the basic pathogenesis is spleen and stomach dysfunction, functional disorders, stomach stagnation, spleen deficiency qi stagnation, spleen qi in the treatment, traditional Chinese medicine has its unique advantage in the treatment of FD. This study by in vitro and in vivo intervention FD spleen deficiency disease combined with syndrome rat model by using Jianpi prescription, study its mechanism of action. Objective: 1. in vivo pharmacodynamics and pharmacology experiment of spleen Decoction No.1 and observe the curative effect of Six Gentlemen Decoction. Jianpi prescription combined with gastrointestinal motility in rats with spleen deficiency of FD, to explore the possible mechanism of treatment of FD; 2. in vitro under the condition of FD of spleen deficiency disease combined with syndrome model rats with different doses of Jianpi prescription intervention, to explore the effect of Jianpi Recipe on direct rats in different parts of gastric tissue of gastric motility the direct effect; body under the condition of different composition in different parts of the spleen and stomach tissue of gastric motility observed from 3.. The contents of Experiment 1, establishment and evaluation of rat models of spleen deficiency combined with FD Objective: to establish and evaluate FD combination of disease and syndrome of spleen deficiency rats model of materials and methods: 30 male SD rats (rats) were randomly divided into normal group, simple iodoacetamide gavage group (disease group), intragastric administration of iodoacetamide superimposed small platform group (standing group of combined disease and syndrome), born 7 days of purchase, 3 days of adaptive feeding. 10 day old male SD rats, normal group Daily with 2% sucrose solution by gavage; model group daily with 0.1% iodoacetamide solution by gavage, each 0.2ml, by gavage for 6 days; when rats were 3 weeks old, were removed, cage, to rats after 6 weeks of age, continue to give the normal rat diet; iodoacetamide superimposed small standing group per day platform 18:00-8:00 is a small platform to stand for 14 consecutive days. After the modeling, in general, were observed in body weight, food intake, water intake, grip strength, sucrose preference, serum lactic acid, D- xylose, amylase content. Results: (1) general situation: the combination of disease and syndrome model rats, weight, food intake. The amount of water compared with the normal model group and disease group, was significantly lower (P0.05). (2) determination of grip: Rats Model grip strength significantly decreased compared with the normal group and disease group model combining disease with syndrome (P0.05). (3) sucrose preference: the model group rats decreased in syrup the consumption of combined disease and syndrome, but The normal model group and disease group were compared, the difference was not statistically significant (P0.05). (4) serum index: compared with the normal group and disease model group, model group serum D- xylose combined disease, amylase content was significantly reduced (P0.05), serum lactic acid content increased significantly (P0.01). In experiment two, Jianpi Recipe on FD spleen deficiency rat model with the objective of research body gastrointestinal motility mechanism: To observe the effect of spleen deficiency 1 recipe and the curative effect of Six Gentlemen Decoction on gastrointestinal motility in FD rats with spleen deficiency syndrome, from the gastric emptying, intestinal propulsion test and serum gastrointestinal hormone levels to explore the possible mechanism of treatment of FD materials and methods. PingTai Railway Station: take iodoacetamide superimposed small legislation to establish FD spleen deficiency disease combined with syndrome rat model, the experimental animal were randomly divided into normal group, model group, western medicine group (domperidone group), spleen 1 Fang Gao dose group, middle dose group, low dose group, 棣欑爞鍏悰瀛愰珮鍓傞噺緇，

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