本文關(guān)鍵詞：補中益氣湯“益氣升陽”配伍治療脾虛泄瀉大鼠的作用機制研究　出處：《廣州中醫(yī)藥大學》2016年碩士論文　論文類型：學位論文

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【摘要】：目的：補中益氣湯出自李東垣《脾胃論》,為益氣升陽法代表方,是臨床上治療脾虛泄瀉證的常用處方。本實驗基于病理組織及營養(yǎng)物質(zhì)吸收的角度,復制脾虛泄瀉證動物模型,探討脾虛泄瀉的發(fā)生及其發(fā)生葡萄糖吸收障礙可能的作用機制；并通過補中益氣湯“益氣升陽”各配比組方進行干預,明確補中益氣湯中益氣升陽配比“黃芪-升麻、柴胡”的最佳用量。通過實驗研究挖掘其科學內(nèi)涵,為臨床醫(yī)家運用該方起指導作用。方法：1.補中益氣湯益氣升陽配比組方對脾虛泄瀉大鼠的影響通過多因素法“五味偏食+游泳力竭+控制飲食”建立脾虛泄瀉大鼠模型,造模完成后,隨機分成補中益氣湯組、補中益氣湯倍“升麻-柴胡”組及補中益氣湯去“升麻-柴胡”組,分別予以相對應的藥物進行干預,考察大鼠體重、宏觀積分、胸腺指數(shù)及脾臟指數(shù)。2.補中益氣湯益氣升陽配比組方對脾虛泄瀉大鼠小腸粘膜修復的影響通過多因素法“五味偏食+游泳力竭+控制飲食”建立脾虛泄瀉大鼠模型,造模完成后,隨機分成補中益氣湯組、補中益氣湯倍“升麻-柴胡”組及補中益氣湯去“升麻-柴胡”組,分別予以相對應的藥物進行干預,通過光鏡下觀察小腸絨毛結(jié)構(gòu),并運用醫(yī)學影像分析系統(tǒng)測量小腸絨毛高度及寬度,以及透射電鏡觀察小腸微絨毛結(jié)構(gòu)。3.補中益氣湯益氣升陽配比組方對脾虛泄瀉大鼠葡萄糖轉(zhuǎn)運體GLUT2相關(guān)基因表達的影響通過多因素法“五味偏食+游泳力竭+控制飲食”建立脾虛泄瀉大鼠模型,造模完成后,隨機分成補中益氣湯組、補中益氣湯倍“升麻-柴胡”組及補中益氣湯去“升麻-柴胡”組,分別予以相對應的藥物進行干預后提取小腸粘膜總RNA,運用RT-PCR法檢測葡萄糖轉(zhuǎn)運吸收相關(guān)基因GLUT2、Na+-K+-ATPase、T1R2+T1R3、Cavl.3、PKC-β-ⅡI亞型基因的表達。成果：1.體重、宏觀積分及胸腺、胰臟指數(shù)：模型組大鼠體重明顯下降,宏觀積分明顯上升(P0.05)。胸腺指數(shù)及脾臟指數(shù)明顯下降(P0.05)；補中益氣湯組體重、胸腺指數(shù)、脾臟指數(shù)均明顯上升,宏觀積分下降(P0.05)。而其他兩組一些指標上改變不明顯。(P0.05)2.病理學檢測：模型組大鼠小腸絨毛形態(tài)破壞,炎癥細胞浸潤,上皮細胞缺失；細胞器破壞,小腸絨毛的高度及寬度均明顯降低(P0.01)。經(jīng)補中益氣湯干預后補中益氣湯組小腸粘膜修復明顯,絨毛的高度及寬度均可見升高(P0.01)。而倍“升麻-柴胡”組及去“升麻-柴胡”組病理學上改變不明顯(P0.05)。3.葡萄糖轉(zhuǎn)運吸收相關(guān)基因：模型組腸道粘膜GLUT2、Na+-K+-ATP酶、PKC-β-Ⅱ亞型表達量明顯降低(P0.05)。TIR2、T1R3及Cavl.3表達量亦明顯降低(P0.05)。經(jīng)補中益氣湯不同配比組方干預后,各組脾虛泄瀉大鼠模型基因表達均有所升高。其中,補中益氣湯原方組,各基因的表達量均明顯升高(P0.01)。而倍“升麻-柴胡”組及去“升麻-柴胡”組升高不明顯(P0.05)。結(jié)論：脾虛泄瀉大鼠一般狀態(tài)變化、體重、胸腺指數(shù)、脾臟指數(shù)下降；小腸絨毛損傷；腸道粘膜葡萄糖轉(zhuǎn)運吸收相關(guān)基因表達下降,從而證實了脾虛泄瀉的發(fā)生與葡萄糖吸收障礙相關(guān),且與腸道粘膜上PKC-β-Ⅱ-GLUT2-TIR2、T1R3/Cav1.3通道密切相關(guān)。而補中益氣湯通過改善小腸粘膜,提升該通道基因表達,從而達到治療脾虛泄瀉；其中,尤以補中益氣湯原方配伍為最佳,進一步證實了補中益氣湯益氣升阻的配伍應當為益氣藥與升陽藥共用,并且大劑量的益氣藥與小劑量的升陽藥的配伍更能體現(xiàn)其益氣升陽功效。
[Abstract]:Objective: Buzhong Yiqi Decoction on spleen and stomach from Li Dongyuan < >, as the representative prescription Yiqi Shengyang method, is commonly prescribed in clinical treatment of diarrhea of spleen deficiency. The pathological tissue and nutrient absorption based on the angle of diarrhea of spleen deficiency animal model replication, to explore possible mechanism and absorption of glucose disorder of spleen deficiency diarrhea; and through BUZHONGYIQITANG "Yiqi Shengyang" the proportion of prescription intervention, clear BUZHONGYIQITANG in the proportion of "Huangqi Yiqi Shengyang - Cimicifuga, bupleurum optimal dosage". Through the experimental study to explore its scientific connotation, guiding role for clinical doctors use the party. Methods: 1. effects of Buzhong Yiqi Decoction prescription of Yiqi Shengyang ratio spleen deficiency diarrhea rats with spleen deficiency diarrhea rat model was established by the method of multi factors "five kinds of diet + swimming + diet", after modeling, were randomly divided into fill in Yiqi Decoction, Buzhongyiqi Decoction times "Cimicifuga - Bupleurum group and Buzhongyiqi Decoction to" Cimicifuga Bupleurum chinense "group, respectively, to the corresponding drug intervention study, rats, macro integral effect, the index of thymus and spleen.2. Buzhongyiqi Decoction Yiqi Shengyang combination ratio on the repair of intestinal mucosa in diarrhea of spleen deficiency rat spleen deficiency diarrhea rat model established by the method of multi factors" five kinds of diet + swimming + diet ", after modeling, were randomly divided into BUZHONGYIQITANG group, BUZHONGYIQITANG times" Cimicifuga - Bupleurum group and Buzhongyiqi Decoction to "Cimicifuga Bupleurum chinense" group, respectively received drug intervention correspondingly, by observation under light microscope, the structure of the intestinal villi, and the use of medical image analysis system to measure the villus height and width, and the TEM microvilli structure.3. BUZHONGYIQITANG Yiqi Shengyang ratio group Influence on related gene expression in rats with spleen deficiency diarrhea glucose transporter GLUT2 of spleen deficiency rat model was established by the method of multi factors "five kinds of diet + swimming + diet", after modeling, were randomly divided into BUZHONGYIQITANG group, BUZHONGYIQITANG times "Cimicifuga - Bupleurum group and Buzhongyiqi Decoction to" Cimicifuga - Bupleurum "group, respectively, to the corresponding drug intervention after extracting total RNA of intestinal mucosa, detected by using the RT-PCR method to absorb glucose transport related genes GLUT2, Na+-K+-ATPase, T1R2+T1R3, Cavl.3, expression of PKC- beta II subtype I gene. Results: 1. body weight, thymus index and macro integration, pancreas weight the rats in the model group decreased significantly, the macro integral increased significantly (P0.05). The index of thymus and spleen decreased significantly (P0.05); BUZHONGYIQITANG group weight, thymus index, spleen index were significantly increased and the macroscopic score decreased (P0 .05). And the other two groups did not change significantly. Some indexes (P0.05) detected 2. pathology: failure modes of small intestine villi of the rats in the model group, the infiltration of inflammatory cells and epithelial cell loss; organelle damage, the height and width of intestinal villi were significantly decreased (P0.01). The BUZHONGYIQITANG group of small intestinal mucosa repair Zhongyi Qi Decoction after the intervention was repaired, the height and width of the villi were found increased (P0.01). And the times "- group and Cimicifuga Bupleurum" to "Cimicifuga pathology - Bupleurum group did not change significantly (P0.05).3. glucose transporter gene related to absorption of intestinal mucosal GLUT2: model group, Na+-K+-ATP enzyme, PKC- beta II subtype expression was lower (P0.05).TIR2, T1R3 and Cavl.3 expression also decreased significantly (P0.05). The different ratio of BUZHONGYIQITANG intervention group, each group of rats with spleen deficiency diarrhea gene increased. Among them, Buzhongyiqi Decoction group, respectively Gene expression levels were significantly increased (P0.01). And the times "Cimicifuga - Chaihu" group and "Cimicifuga Bupleurum chinense was not elevated group (P0.05). Conclusion: the changes of general condition, spleen deficiency diarrhea rat body weight, thymus index, spleen index decreased; intestinal villus injury; intestinal mucosal absorption of glucose transporter gene the expression decreased, thus confirming the occurrence of diarrhea of spleen deficiency and glucose absorption and intestinal mucosal barrier, PKC- beta II -GLUT2-TIR2, T1R3/Cav1.3 channels are closely related. And Buzhongyiqi Decoction by improving intestinal mucosa, enhance the channel gene expression, so as to achieve the treatment of spleen deficiency diarrhea; among them, especially in Buzhongyiqi decoction for compatibility the best, further confirmed the compatibility of BUZHONGYIQITANG lift drag should be shared as Qi Qi medicine and sun medicine, and sun Qi medicine compatibility of high dose and low dose of which can reflect more benefits Gas sun effect.

【學位授予單位】：廣州中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R256.34

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