本文關(guān)鍵詞：陽(yáng)虛便秘動(dòng)物模型的建立及濟(jì)川煎治療作用研究　出處：《山西省中醫(yī)藥研究院》2017年碩士論文　論文類(lèi)型：學(xué)位論文

  更多相關(guān)文章： 陽(yáng)虛便秘 動(dòng)物模型 濟(jì)川煎 作用機(jī)制

【摘要】：目的建立大鼠陽(yáng)虛便秘動(dòng)物模型,并在此基礎(chǔ)上對(duì)濟(jì)川煎治療陽(yáng)虛便秘的作用及作用機(jī)制進(jìn)行初步的探討研究。方法關(guān)于陽(yáng)虛便秘病證結(jié)合動(dòng)物模型建立部分:用一組大鼠按照文獻(xiàn)方法即食用白醋加活性炭冰水作為造模因素來(lái)制作大鼠陽(yáng)虛便秘動(dòng)物模型,用另外一組大鼠按照改進(jìn)文獻(xiàn)方法以后即4℃食用白醋加活性炭冰水再加上止瀉藥物復(fù)方地芬諾酯的辦法建立大鼠陽(yáng)虛便秘動(dòng)物模型,并設(shè)置空白對(duì)照組。然后分別在造模因素停止后第1天和去除造模因素后第7天對(duì)各組大鼠同時(shí)進(jìn)行檢測(cè)評(píng)價(jià)分析,具體檢測(cè)從以下幾方面進(jìn)行:觀察實(shí)驗(yàn)大鼠在模型建立過(guò)程中的一般狀態(tài)并進(jìn)行評(píng)分記錄,觀察實(shí)驗(yàn)大鼠首粒排便時(shí)間和排便粒數(shù),用生物機(jī)能測(cè)定儀檢測(cè)實(shí)驗(yàn)大鼠的結(jié)腸肌電改變,用酶聯(lián)免疫吸附法對(duì)實(shí)驗(yàn)大鼠體內(nèi)乙酰膽堿酯酶(Ach E)、胃動(dòng)素(MTL)、生長(zhǎng)抑素(SS)、環(huán)磷酸腺苷(c AMP)、環(huán)磷酸鳥(niǎo)苷(c GMP)、蛋白激酶A(PKA)、蛋白激酶C(PKC)的含量變化進(jìn)行檢測(cè)。最后對(duì)所得數(shù)據(jù)用SPSS16.0進(jìn)行統(tǒng)計(jì)分析得出結(jié)論。有關(guān)濟(jì)川煎治療陽(yáng)虛便秘作用及其機(jī)制初步研究部分:復(fù)制上述改進(jìn)文獻(xiàn)方法后的陽(yáng)虛便秘動(dòng)物模型,然后對(duì)其進(jìn)行隨機(jī)分組,分別為模型組、陽(yáng)性藥物對(duì)照組、濟(jì)川煎高(8.63g/kg)、中(4.31g/kg)、低(2.16g/kg)劑量組,加之空白對(duì)照組共計(jì)6組。陽(yáng)性藥物對(duì)照組大鼠使用莫沙必利進(jìn)行治療,濟(jì)川煎高、中、低劑量組大鼠分別使用濟(jì)川煎的相應(yīng)劑量進(jìn)行灌胃治療,空白對(duì)照組和模型組大鼠在此期間給予同等劑量的蒸餾水灌胃。在治療給藥結(jié)束后對(duì)各組大鼠同時(shí)進(jìn)行檢測(cè)評(píng)價(jià)分析,具體檢測(cè)項(xiàng)目同上,最后所得數(shù)據(jù)用SPSS16.0進(jìn)行統(tǒng)計(jì)分析得出結(jié)論。結(jié)果關(guān)于動(dòng)物病證結(jié)合模型建立部分:在造模因素停止后第1天,兩模型組大鼠的一般狀態(tài)都較差,均出現(xiàn)了腹脹、體重減輕、皮毛枯槁乍立、倦怠蜷縮、反應(yīng)遲緩、糞便干硬等征象,與空白對(duì)照組相比也都出現(xiàn)了首粒排便時(shí)間后延、排便粒數(shù)減少,結(jié)腸肌電慢波頻率減慢、振幅增大的現(xiàn)象(P㩳0.05或P㩳0.01),也都表現(xiàn)出血漿MTL含量下降,SS水平升高,血清Ach E含量下降,c AMP/c GMP比值降低,下丘腦組織上清中PKA水平下降,PKC水平升高的變化(P㩳0.05或P㩳0.01)。但改進(jìn)文獻(xiàn)方法后的模型組(模型Ⅱ組)大鼠病理狀態(tài)與文獻(xiàn)方法模型組大鼠(模型Ⅰ組)相比其表現(xiàn)則更為明顯。去除造模因素7天后,模型Ⅰ組大鼠基本自愈,精神狀態(tài)、活動(dòng)度、排便狀況、結(jié)腸運(yùn)動(dòng)情況,Ach E、MTL、SS、c AMP/c GMP、PKA、PKC的變化等與空白對(duì)照組大鼠相比幾乎沒(méi)有差別,雖然沒(méi)有恢復(fù)至與空白組大鼠同等水平,但其數(shù)值與空白組大鼠相應(yīng)數(shù)值比較,其差異已經(jīng)沒(méi)有統(tǒng)計(jì)學(xué)意義了。而模型Ⅱ組大鼠病理狀態(tài)依然明顯,各項(xiàng)病理檢測(cè)指標(biāo)與空白對(duì)照組大鼠相比其差異依然具有統(tǒng)計(jì)學(xué)意義(P㩳0.05或P㩳0.01)。關(guān)于濟(jì)川煎治療陽(yáng)虛便秘作用及其機(jī)制初步探討部分:濟(jì)川煎高、中劑量組大鼠一般狀態(tài)恢復(fù)較好,相比較于模型組大鼠其體重也有所增長(zhǎng),同時(shí)首粒排便時(shí)間縮短,排便粒數(shù)增加,結(jié)腸肌電慢波頻率加快、振幅下降(P㩳0.05或P㩳0.01),血漿MTL含量升高,SS水平下降,血清Ach E含量升高,c AMP/c GMP比值上升,下丘腦組織上清中,PKC水平降低,與模型組相比有顯著差異(P㩳0.05或P㩳0.01)。濟(jì)川煎低劑量組大鼠的狀態(tài)與模型組大鼠相比有所改善,但沒(méi)有顯著差異。陽(yáng)性藥物對(duì)照組大鼠狀態(tài)的改善則僅限于便秘相關(guān)方面,如與模型組大鼠相比首粒排便時(shí)間縮短、排便粒數(shù)增加,結(jié)腸肌電慢波頻率升高,振幅降低,血漿MTL含量升高,SS水平下降(P㩳0.05或P㩳0.01)等,而其皮毛色澤、精神狀態(tài)、體重的改變則不大,c AMP/c GMP比值、PKC水平的變化與模型組大鼠相比則沒(méi)有差異。結(jié)論4℃白醋、活性炭冰水加復(fù)方地芬諾酯灌胃可建立起比較穩(wěn)定的陽(yáng)虛便秘動(dòng)物模型,模型動(dòng)物的病理特征與陽(yáng)虛便秘的臨床癥狀相類(lèi)似,并存在腸神經(jīng)遞質(zhì)和胃腸激素分泌混亂。濟(jì)川煎高、中劑量組能不同程度地改善陽(yáng)虛便秘模型大鼠的各項(xiàng)癥狀指征,其作用機(jī)制考慮可能與其影響環(huán)核苷酸、蛋白激酶、腸神經(jīng)遞質(zhì)和胃腸激素變化有關(guān)。
[Abstract]:Objective to establish a rat animal model of Yang deficiency and constipation, were preliminary studied the effect and mechanism of action and on the basis of Jekawa in the treatment of Yang deficiency and constipation. Methods of Yang deficiency and constipation disease combined with syndrome animal model: one group of rats according to the method of instant white vinegar and activated carbon as the ice model to produce a large the rat animal model of Yang deficiency and constipation, with another group of rats after the improved method is in accordance with the literature 4 C vinegar plus charcoal ice plus antidiarrheal drug compound diphenoxylate to establish rat animal model of Yang deficiency and constipation, and set the blank control group. Then the rats in the first days after the removal of stop factors and model after seventh days of rats in each group were detected at the same time analysis, specific detection from the following aspects: the rats were observed in the model building process and the general state The score records, observed the first defecation time and defecation grain grain number, change the colonic electromyography measurement instrument detection of biological function of experimental rats, rats of acetylcholinesterase in vivo by enzyme-linked immunosorbent assay (Ach E), motilin (MTL), somatostatin (SS), cyclic adenosine monophosphate (C AMP), cyclic guanosine monophosphate (C GMP), protein kinase A (PKA), protein kinase C (PKC) contents were detected. Finally the data were analyzed by SPSS16.0. The conclusion part Jichuanjian treatment effect and mechanism of Yang deficiency and constipation: a preliminary study on animal model of Yang deficiency and constipation of the improved method of literature after then, were randomly assigned to it, respectively, model group, positive drug group, Jekawa Ta (8.63g/kg), in (4.31g/kg) (2.16g/kg), low dose group and blank control group, a total of 6 groups. The positive drug control group rats using mosapride in For treatment, the corresponding Jichuanjian high dose and low dose groups of rats were used Jichuanjian by intragastric administration of distilled water during the treatment, the control group and model group rats were then given the same dose of intragastric administration in the treatment. After the end of the rats were detected at the same time analysis, specific test items above, finally, the data statistical analysis using SPSS16.0 model. The results of part of the combination of disease and syndrome animal model: in the stop after first days, the general state of the two rats in the model group were poor, there were abdominal distension, weight loss, haggard fur first, burnout curled up, slow response, dry hard stool signs, compared with the control group also appeared in the first time of defecate after the extension, the number of defecate decreases, colonic electromyography decrease of slow wave frequency, amplitude increased (P? 0.05 or P? 0.01), also showed a decrease in plasma MTL content SS, elevated levels of serum Ach, decrease the content of E, C, AMP/c and GMP ratio decreased, the level of PKA in hypothalamus was decreased, PKC levels increased (P? 0.05 or P? 0.01). But the improvement method of literature model group (model II Group) rats pathological state and method of literature model group rats (model group) compared to its performance is more obvious. The removal model for 7 days, model group rats basic self-healing, mental state, activity, defecation condition, colonic motility, Ach, E, MTL, SS, C AMP/c GMP, PKA, PKC change compared to almost no difference with the rats in control group, although not recovered with the blank group the same level, but the value of the rats in the blank group the corresponding numerical comparison, the difference was not statistically significant. The pathological state of rat model of group II is still obvious, the pathological detection index and the rats in control group compared the difference in However, with statistical significance (P? 0.05 or P? 0.01). And to explore the mechanism of treatment of constipation: part Jichuanjian Yang Jichuanjian high dose group, the general condition of rats recovered well, compared with the model rats, the body weight also increased, while the first defecate time, defecate number increase, colon myoelectric slow wave frequency speed, the amplitude decreased (P? 0.05 or P? 0.01), plasma MTL increased and SS level decreased, serum Ach content of E, C AMP/c GMP ratio was increased, the hypothalamus in the supernatant of PKC decreased, there was significant difference compared with the model group (P? 0.05 or P? 0.01 Jichuanjian). Low dose group rats status improved compared with the model rats, but no significant difference. To improve the positive drug control group in rats is limited to constipation related aspects, such as the first grain of defecation was shortened compared with the rats in the model group, the number of defecate increase, Colonic myoelectric slow wave frequency increases, the amplitude decreased, plasma MTL increased and SS decreased (P? 0.05 or P? 0.01), but their fur color, mental state, weight change is small, the ratio of GMP C AMP/c, PKC level and the changes of rats in the model group compared with no difference. Conclusion 4 C white vinegar, activated carbon and water compound diphenoxylate gavage can establish stable animal model of Yang deficiency and constipation, clinical symptoms and pathological features of Yang deficiency and constipation animal models are similar, and the existence of intestinal neurotransmitters and gastrointestinal hormone secretion disorder. Jichuanjian high dose group could improve the symptoms of Yang deficiency constipation model rat indications, considering its mechanism of action may be related to its effect of cyclic nucleotide, protein kinase, intestinal neurotransmitters and gastrointestinal hormones.

【學(xué)位授予單位】：山西省中醫(yī)藥研究院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R285.5;R-332

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