【摘要】：目的:功能性消化不良(Funtional dyspepsia,FD)是十分普遍的消化系統(tǒng)疾病。依據(jù)中醫(yī)學理論,功能性消化不良餐后不適綜合征屬于"痞滿"范疇,上腹痛綜合征則屬于"胃痛"的范疇。為從整體上把握對胃痛的認識,了解數(shù)據(jù)挖掘技術(shù)及其在中醫(yī)藥研究的運用,本研究對胃痛病因病機、辨證論治的相關(guān)文獻進行了整理;并對數(shù)據(jù)挖掘概念和其在中醫(yī)藥領(lǐng)域運用現(xiàn)狀的文獻進行了分析。為系統(tǒng)了解國內(nèi)外功能性消化不良機制以及其中的內(nèi)臟高敏感性機制研究現(xiàn)狀,我們對相關(guān)文獻進行了整理和綜述。為展現(xiàn)胃痛(FD)的證型特征,對胃痛(FD)的病案資料進行了證型數(shù)理統(tǒng)計;為指導(dǎo)臨床胃痛(FD)的治療提供客觀依據(jù),利于學術(shù)經(jīng)驗傳承,對黃穗平教授治療胃痛(FD)的用藥特點進行了數(shù)據(jù)挖掘。為了探究脾虛證功能性消化不良內(nèi)臟高敏感性的機制以及健脾藥物的治療機制,在蛋白表達水平和基因轉(zhuǎn)錄水平為中藥治療作用提供客觀和定量的指標,建立了脾虛證功能性消化不良的內(nèi)臟高敏感性模型;在我們既往研究的基礎(chǔ)上,結(jié)合病案研究結(jié)果,選擇健脾方四君子湯進行干預(yù)。方法:臨床研究以2015年6月-2016年6月于廣東省中醫(yī)院黃穗平教授處治療胃痛的門診病例為信息來源,篩選出胃痛(FD)病歷,對原始資料進行數(shù)據(jù)整理,建立了規(guī)范化的Excel胃痛證治數(shù)據(jù)庫。以此為基礎(chǔ),采用SPSS19.0和Clementine12.0軟件,運用頻數(shù)分析、關(guān)聯(lián)規(guī)則和因子分析分析胃痛(FD)證治數(shù)據(jù)。根據(jù)統(tǒng)計結(jié)果,進行胃痛(FD)基線特征、證型分布、常用藥物、常用藥物配伍和藥證關(guān)系的分析,總結(jié)治療特點。實驗研究以SD雄性大鼠為研究對象,共36只,隨機分為空白組、模型組、四君子湯組、莫沙必利組,每組各9只。空白組不予造模,其余三組采用碘乙酰胺+站小平臺法+隔日禁食,建立脾虛證FD內(nèi)臟高敏感性大鼠模型。空白組和模型組給予生理鹽水灌胃,中藥組給予四君子湯灌胃,西藥組給予莫沙必利灌胃,共用藥14天。觀測各組大鼠癥狀、體重;記錄反應(yīng)胃感覺運動的肌電圖;運用免疫組化技術(shù)、熒光定量聚合酶鏈式反應(yīng)(Real-time PCR)技術(shù)測量胃竇組織神經(jīng)生長因子(NGF)、磷酯酶Cγ(PLC Y)和瞬時受體電位辣椒素亞型1(TRPV1)通道的表達。結(jié)果:臨床研究門診胃痛(FD)患者中,中青年人占89.65%;女性占73.16%。病因以飲食因素最多;共出現(xiàn)12個胃痛(FD)證型,最多的證型是脾虛氣滯。黃穗平教授辨治胃痛(FD)最常用的10味藥物是黨參、木香、法半夏、延胡索、炙甘草、陳皮、白術(shù)、砂仁、茯苓、厚樸;本研究挖掘出黃教授的19個常用藥對,6個常用五味藥物組合,3個證型與藥物的相關(guān)組合。因子分析共顯示7個公因子,其中有意義的公因子是4個,分別是在白術(shù)、山藥、炒白術(shù)、白扁豆具有較大的載荷的第二個公因子;在茯苓、茯神、合歡皮具有較大的載荷的第三個公因子;在厚樸、海螵蛸、枳實具有較大的載荷的第六個公因子;在桔梗具有較大的載荷的第七個公因子。實驗研究脾氣虛型造模后,大鼠蜷縮,懶動,反應(yīng)較遲鈍,毛發(fā)枯槁,大便欠成形,體重明顯減輕,符合中醫(yī)脾虛證的表現(xiàn)。治療后,中西藥組大鼠活動較活躍,反應(yīng)遲鈍改善,毛發(fā)色澤變亮,大便成形,脾虛癥狀得到改善。造模后脾虛證FD內(nèi)臟高敏感模型大鼠體重明顯低于正常組大鼠,差異有統(tǒng)計學意義(P0.05),模型各組大鼠體重無顯著差異。藥物干預(yù)后,四君子湯組大鼠平均體重較模型組升高,但差異無統(tǒng)計學意義(P0.05);莫沙必利組大鼠體重與模型組差異無統(tǒng)計學意義(P0.05)。記錄反應(yīng)胃感覺運動的肌電圖顯示,相比空白組,模型組大鼠肌電圖波幅出現(xiàn)相對較大的增加,符合FD內(nèi)臟高敏感性肌電圖變化。治療后,相比模型組,治療組的肌電圖波幅增加變小,中藥組的波幅變化與正常組相近,從趨勢上顯示四君子湯降低了內(nèi)臟高敏感性。免疫組化結(jié)果顯示NGF、PLCγ、TRPV1在細胞質(zhì)表達。在蛋白表達水平,與空白組對照,模型組NGF出現(xiàn)陽性表達增加,兩者的差異具有統(tǒng)計學意義(P0.05);藥物治療后,NGF出現(xiàn)陽性表達減少,但是不存在統(tǒng)計學差異(P0.05);西藥組與中藥組的表達差異不存在統(tǒng)計學意義(P0.05)。在蛋白表達水平,與空白組對照,模型組PLCγ出現(xiàn)陽性表達增加,具有統(tǒng)計學差異(P0.05);藥物治療后,PLCγ出現(xiàn)陽性表達減少,其中中藥組與模型組的差異具有統(tǒng)計學意義(P0.05);中藥組和西藥組差異無統(tǒng)計學意義(P0.05)。在蛋白表達水平,與空白組對照,模型組TRPV1出現(xiàn)陽性表達增加,具有統(tǒng)計學差異(P0.05);藥物治療后,TRPV1出現(xiàn)陽性表達減少,中藥組與模型組的差異具有統(tǒng)計學意義(P0.05);中藥組和西藥組差異無統(tǒng)計學意義(P0.05)。在mRNA轉(zhuǎn)錄水平,相比空白組,模型組的PLCγ、TRPV1 mRNA表達水平顯著上調(diào),具有統(tǒng)計學差異(P0.05);在藥物治療后,西藥組和中藥組出現(xiàn)PLCγ、TRPV1 mRNA表達水平下調(diào),與模型組對照,西藥組表達水平下調(diào)無統(tǒng)計學差異(P0.05),中藥組表達水平下調(diào)則存在顯著統(tǒng)計學差異(P0.05);中藥組和西藥組差異無統(tǒng)計學意義(P0.05)。結(jié)論:臨床研究門診胃痛(FD)患者以中青年人和女性居多;飲食因素是重要的病因;胃痛(FD)證型以脾虛氣滯證最多。黃穗平教授治療胃痛(FD)最常用健脾藥、理氣藥、活血止痛藥、祛濕藥;其常用藥對既有獨特的藥物組合,又有四君子湯、六君子湯、異功散、香砂六君子湯方劑的藥物組合運用;其治療胃痛(FD)代表方劑為六君子湯或香砂六君子或兩者分別合延胡索加減;其治療胃痛(FD)的脾虛氣滯證以香砂六君子湯為底方,肝郁脾虛證以逍遙散為底方,脾胃虛寒證以理中湯合四君子湯為底方。因子分析分別展現(xiàn)黃教授在治療脾虛濕盛、失眠、胃脹滿、反酸和咽病方面獨特用藥規(guī)律。黃穗平教授治療胃痛(FD)的主要特點可概括為探求病因、補益脾胃、理氣止痛、祛濕清熱。實驗研究NGF-PLC γ-TRPV1信號通路可能參與了脾虛型FD的內(nèi)臟高敏感發(fā)生。四君子湯可能通過PLC-TRPV1信號通路降低脾虛型FD內(nèi)臟高敏感性,從而起治療作用。
[Abstract]:Objective: Functional dyspepsia (FD) is a very common digestive system disease. According to the theory of traditional Chinese medicine, functional dyspepsia postprandial discomfort syndrome belongs to the category of "fullness" and epigastralgia syndrome belongs to the category of "stomachache". In order to systematically understand the mechanism of functional dyspepsia and the visceral hypersensitivity mechanism, we summarized the related literatures on the etiology, pathogenesis, syndrome differentiation and treatment of gastralgia. In order to show the characteristics of syndromes of gastralgia (FD), the data of syndromes of gastralgia (FD) were analyzed by mathematical statistics, and to provide objective basis for guiding the treatment of clinical gastralgia (FD) and facilitate the transmission of academic experience, the medication characteristics of Professor Huang Suiping in treating gastralgia (FD) were analyzed by data mining. The mechanism of visceral hypersensitivity in dyspepsia and the therapeutic mechanism of invigorating spleen drugs provide objective and quantitative indexes for the therapeutic effect of traditional Chinese medicine at protein expression level and gene transcription level. Methods: From June 2015 to June 2016, the outpatient cases of stomachache treated by Professor Huang Suiping of Guangdong Hospital of Traditional Chinese Medicine were selected as the information source. The original data were sorted out and a standardized Excel database of stomachache syndrome and treatment was established. Based on the statistical results, the baseline characteristics of gastralgia (FD), the distribution of syndromes, the relationship between common medicines, compatibility of common medicines and syndromes were analyzed, and the therapeutic characteristics were summarized. There were 9 rats in each group: blank group, model group, Sijunzi Decoction group and Mosapride group. No model was made in blank group, and the other three groups were given iodoacetamide + small platform + fasting every other day to establish visceral hypersensitivity model of FD with spleen deficiency syndrome. Sapride was administered intragastrically for 14 days. Symptoms, body weight, electromyogram (EMG) reflecting gastric sensory movement, and the expression of nerve growth factor (NGF), phospholipase C gamma (PLC Y) and transient receptor potential capsaicin subtype 1 (TRPV1) channels in antral tissues were measured by immunohistochemistry and Real-time PCR. Results: Among the patients with stomachache (FD), 89.65% were young and middle-aged, 73.16% were females. In this study, 19 common drug pairs, 6 common five-flavor drug combinations, and 3 syndromes and drug combinations were excavated. Shen, Albizzia julibrissin bark has the third common factor of greater load; in Magnolia officinalis, Octopus, Fructus Aurantii has the sixth common factor of greater load; in Platycodon grandiflorum has the seventh common factor of greater load. After the experimental study of the model of spleen-qi deficiency, the rats curled up, lazy, slow reaction, hairy and hairy, feces underformed, weight significantly reduced, accord with. After treatment, the rats in the traditional Chinese and Western medicine group were more active, their reactions were improved, their hair color became brighter, stool formed, and spleen deficiency symptoms were improved. After drug intervention, the average weight of rats in Sijunzi Decoction group was higher than that in model group, but the difference was not statistically significant (P 0.05). There was no significant difference in body weight between Mosapride group and model group (P 0.05). After treatment, compared with the model group, the EMG amplitude of the treatment group increased and decreased, and the amplitude of the traditional Chinese medicine group was similar to that of the normal group. The trend showed that Sijunzi Decoction decreased the visceral hypersensitivity. Compared with the control group, the positive expression of NGF increased in the model group, and the difference was statistically significant (P 0.05); After drug treatment, the positive expression of NGF decreased, but there was no statistical difference (P 0.05); There was no statistical significance between the Western medicine group and the Chinese medicine group (P 0.05). The positive expression of PLC-gamma was increased, with a statistical difference (P 0.05); after drug treatment, the positive expression of PLC-gamma decreased, and the difference between the traditional Chinese medicine group and the model group was statistically significant (P 0.05); there was no significant difference between the traditional Chinese medicine group and the western medicine group (P 0.05). There was statistical difference (P 0.05); TRPV1 positive expression decreased after drug treatment, the difference between the Chinese medicine group and the model group was statistically significant (P 0.05); There was no significant difference between the Chinese medicine group and the western medicine group (P 0.05). In the mRNA transcription level, compared with the blank group, the expression level of PLC gamma and TRPV1 mRNA in the model group was significantly up-regulated, with statistical difference (P 0.0). 5) After drug treatment, the expression levels of PLC-gamma and TRPV1 mRNA were down-regulated in the western medicine group and the Chinese medicine group. Compared with the model group, there was no significant difference (P 0.05) in the western medicine group, but there was significant difference (P 0.05) in the Chinese medicine group. Conclusion: There was no significant difference between the Chinese medicine group and the western medicine group (P 0.05). Most of the patients with gastralgia (FD) are young and middle-aged women; dietary factors are important causes; the most common types of gastralgia (FD) are spleen-deficiency and Qi-stagnation syndrome. Professor Huang Suiping is the most commonly used Spleen-strengthening drug, Qi-Regulating drug, blood-activating analgesic drug, and Dampness-eliminating drug in the treatment of gastralgia (FD); his common medicines include not only a unique combination of drugs, but also Sijunzi decoction, Liujunzi decoction, Yigong powder, Xiangsha Liu The representative prescription of treating stomachache (FD) is Liujunzi Decoction or Xiangsha Liujunzi Decoction or both of them are added and subtracted by Yanhusuo respectively; the basic prescription of treating stomachache (FD) is Xiangsha Liujunzi Decoction for spleen deficiency and Qi stagnation, Xiaoyao powder for liver depression and spleen deficiency, Lizhong Decoction for spleen-stomach deficiency and cold, and Sijunzi Decoction for factor. The main characteristics of Professor Huang Suiping's treatment of gastralgia (FD) can be summarized as exploring the etiology, tonifying the spleen and stomach, regulating qi and relieving pain, dispelling dampness and clearing heat. Experimental study on NGF-PLC gamma-TRPV1 signaling pathway may be involved in the visceral hypersensitivity of FD of spleen deficiency type. Sijunzi Decoction may reduce the visceral hypersensitivity of FD of spleen deficiency type through PLC-TRPV1 signaling pathway, thus playing a therapeutic role.
【學位授予單位】：廣州中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R259

【參考文獻】

相關(guān)期刊論文 前10條

1 王慧芬;姚樹坤;劉芳;杜時雨;王淼;張艷麗;;液體營養(yǎng)餐負荷試驗評估功能性消化不良患者胃感覺功能的研究[J];疑難病雜志;2016年05期

2 楊茜;李峰;馬捷;毛萌;吳鳳芝;杜青;張澤靈;尹則陶;李傅堯;;水環(huán)境小平臺建立脾虛證大鼠模型及其評價[J];山東中醫(yī)雜志;2016年05期

3 朱W，

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