本文選題：潰瘍性結(jié)腸炎 + 甘草瀉心湯　； 參考：《南京中醫(yī)藥大學(xué)》2017年博士論文

【摘要】：第一部分甘草瀉心湯對(duì)TNBS結(jié)腸炎模型大鼠的作用機(jī)制研究目的:觀察甘草瀉心湯對(duì)潰瘍性結(jié)腸炎模型大鼠的療效;并研究甘草瀉心湯對(duì)潰瘍性結(jié)腸炎模型大鼠IL-6/STAT3信號(hào)通路中相關(guān)分子的調(diào)節(jié)作用以及對(duì)Claudin-1的調(diào)節(jié)作用。以期揭示其治療潰瘍性結(jié)腸炎的作用機(jī)制及安全效應(yīng)。方法:將60只SD大鼠隨機(jī)分為空白組、模型組、美沙拉嗪組(5-ASA組)、甘草瀉心湯低劑量組(GCXX-L組)、甘草瀉心湯中劑量組(GCXX-M組)和甘草瀉心湯高劑量組(GCXX-H組)6組,每組10只。除空白組外均以TNBS造模,造模后空白組和模型組以生理鹽水灌胃,5-ASA組和甘草瀉心湯各劑量組分別以美沙拉嗪、甘草瀉心湯低、中、高劑量灌胃,治療14天,治療過程中觀察大鼠的一般情況,記錄排便情況及體重變化;14天后從鼠尾靜脈取血,檢測(cè)血清谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)、尿素氮(BUN)、肌酐(Cr)含量,并以ELISA法檢測(cè)外周血中IL-6表達(dá)水平;并對(duì)大鼠肝、腎、結(jié)腸進(jìn)行大體觀察及顯微鏡下病理觀察;以免疫組化分析各組大鼠結(jié)腸組織IL-6、Claudin-1、STAT3及磷酸化STAT3(P-STAT3)的表達(dá);以Real-time PCR法檢測(cè)各組結(jié)腸組織IL-6 mRNA、Claudin-1 mRNA、STAT3 mRNA 的表達(dá)。結(jié)果:與空白組比較,造模后大鼠出現(xiàn)糞便污染肛周皮毛及體重下降現(xiàn)象(P0.01),血清AST含量明顯升高(P0.01),而ALT、BUN、Cr無明顯變化(P0.05);外周血IL-6表達(dá)明顯升高(P0.01);結(jié)腸大體評(píng)分和組織病理評(píng)分明顯增加(P0.01);結(jié)腸組織IL-6、STAT3和P-STAT3蛋白表達(dá)明顯增高(P0.01),而Claudin-1蛋白表達(dá)明顯降低(P0.01);IL-6 和 STAT3 mRNA 表達(dá)明顯增高(P0.01),Claudin-1 mRNA 表達(dá)明顯降低(P0.01)。與模型組比較,經(jīng)美沙拉嗪及甘草瀉心湯治療后,大鼠糞便污染肛周皮毛時(shí)間均有所縮短(P0.01)、體重有所增加(P0.01);除5-ASAZ組外,血清AST含量有所降低(P0.01);外周血IL-6表達(dá)明顯下降(P0.05);除GCXX-L組外結(jié)腸大體評(píng)分和組織病理評(píng)分有所降低(P0.05);結(jié)腸組織IL-6、STAT3和P-STAT3蛋白表達(dá)有所降低(P0.05),Claudin-1蛋白表達(dá)有所增高(P0.05);IL-6和STAT3 mRNA的表達(dá)有所降低(P0.01),Claudin-1 mRNA的表達(dá)有所增高(P0.01)。結(jié)論:甘草瀉心湯能夠明顯改善TNBS潰瘍性結(jié)腸炎大鼠的一般癥狀,減輕結(jié)腸組織損傷及組織結(jié)構(gòu)的改變,且中劑量即可達(dá)到較好效果。甘草瀉心湯作用機(jī)制可能與其降低組織及外周血IL-6表達(dá),抑制IL-6/STAT3信號(hào)轉(zhuǎn)導(dǎo)通路,降低STAT3表達(dá)與活化,增加結(jié)腸Claudin-1表達(dá),恢復(fù)結(jié)腸黏膜機(jī)械屏障等有關(guān)。同時(shí)本實(shí)驗(yàn)未觀察到甘草瀉心湯對(duì)TNBS潰瘍性結(jié)腸炎模型大鼠的肝腎毒性。第二部分甘草瀉心湯聯(lián)合美沙拉嗪對(duì)輕中度潰瘍性結(jié)腸炎的臨床療效觀察目的:初步觀察甘草瀉心湯聯(lián)合美沙拉嗪治療潰瘍性結(jié)腸炎(寒熱錯(cuò)雜證)的療效和安全性。方法:將證屬寒熱錯(cuò)雜的潰瘍性結(jié)腸炎患者37例,隨機(jī)分為治療組19例、對(duì)照組18例。治療組口服甘草瀉心湯,每日1劑,分2次服用,同時(shí)口服美沙拉嗪緩釋顆粒,每次1g,每日4次;對(duì)照組口服美沙拉嗪緩釋顆粒,每次1g,每日4次。兩組均治療4周。比較兩組的療效,以改良Mayo評(píng)分標(biāo)準(zhǔn)及中醫(yī)證候積分分別進(jìn)行評(píng)價(jià),并比較治療前后血常規(guī)及肝腎功能,以觀察其安全性。結(jié)果:治療組脫落2例、對(duì)照組脫落1例患者。治療組總有效率76.5%,對(duì)照組總有效率76.5%,兩組療效無顯著性差異(P0.05);治療組中醫(yī)證候療效總有效率88.3%%,對(duì)照組中醫(yī)證候療效總有效率70.6%,兩組間無顯著性差異(P0.05);治療后兩組改良Mayo評(píng)分均顯著降低(P0.01),但兩組間無顯著差異(P0.05);治療后兩組中醫(yī)證候評(píng)分均顯著降低(P0.01),且治療組明顯低于對(duì)照組(P0.05)。治療前后兩組間白細(xì)胞計(jì)數(shù)(WBC)、紅細(xì)胞計(jì)數(shù)(RBC)、血紅蛋白濃度(Hb)、血小板計(jì)數(shù)(Plt)均無顯著差異(P均0.05)。治療前后兩組間BUN、Cr、ALT、AST水平均無顯著差異(P均0.05)。結(jié)論:甘草瀉心湯聯(lián)合美沙拉嗪用于治療潰瘍性結(jié)腸炎可明顯降低中醫(yī)證候積分,且用藥安全,未見明顯血液系統(tǒng)不良反應(yīng)及肝腎損傷。
[Abstract]:The effect of Glycyrrhiza Xiexin Decoction on TNBS colitis model rats in the first part: To observe the effect of Glycyrrhiza Xiexin Decoction on the rat model of ulcerative colitis, and to study the regulation effect of Glycyrrhiza Xiexin Decoction on the related molecules in the IL-6/STAT3 signaling pathway of ulcerative colitis model rats and the regulation of Claudin-1. Methods: 60 SD rats were randomly divided into blank group, model group, mesalazine group (group 5-ASA), low dose group of Glycyrrhiza Xiexin Decoction (group GCXX-L), dose group of Glycyrrhiza Xiexin Decoction (group GCXX-M) and high dose group (group GCXX-H) of Glycyrrhiza Xiexin Decoction (group GCXX-H), 10 rats in each group, except for the blank group, T After the model was made by NBS, the blank group and the model group were intragastric with normal saline, and the group 5-ASA and Glycyrrhiza Xiexin soup were treated with mesalazine, Glycyrrhiza Xiexin soup low, middle and high dose of the stomach for 14 days. During the treatment, the general condition of the rats was observed, the condition of the defecation and the change of body weight were recorded. After 14 days, the blood was taken from the tail vein of the rat and the serum gluten was detected. The content of transaminase (ALT), AST, BUN and creatinine (Cr), and the expression of IL-6 in the peripheral blood by ELISA, and the gross observation of the liver, kidney and colon in rats and the pathological observation under the microscope; the expression of IL-6, Claudin-1, STAT3 and phosphorylated STAT3 (P-STAT3) in the colon tissues of the rats were analyzed by immunohistochemistry; IME PCR method was used to detect the expression of IL-6 mRNA, Claudin-1 mRNA and STAT3 mRNA in each group. Results: compared with the blank group, there was a decrease in the perianal fur and weight loss (P0.01) in the rats after the model group, and the content of AST in the serum increased significantly (P0.01). The scores of body score and histopathology increased significantly (P0.01), the expression of IL-6, STAT3 and P-STAT3 in colon tissue increased significantly (P0.01), but the expression of Claudin-1 protein decreased significantly (P0.01), IL-6 and STAT3 mRNA increased significantly (P0.01). After treatment, the rats' feces were shortened (P0.01) and body weight increased (P0.01). The serum AST content decreased (P0.01) except the 5-ASAZ group (P0.01), and the expression of IL-6 in peripheral blood decreased significantly (P0.05); the colon gross score and histopathology score decreased (P0.05) except for the GCXX-L group, and IL-6, STAT3 and P-STAT3 protein in the colon tissue. The expression was decreased (P0.05), the expression of Claudin-1 protein increased (P0.05), the expression of IL-6 and STAT3 mRNA decreased (P0.01), and the expression of Claudin-1 mRNA increased (P0.01). Conclusion: Glycyrrhiza Xiexin Decoction can obviously improve the symptoms of TNBS ulcerative colitis rats, reduce the changes of tissue damage and tissue structure of the colon, and the medium agent. The action mechanism of Glycyrrhiza Xiexin Decoction may be related to reducing the expression of IL-6 in tissue and peripheral blood, inhibiting the IL-6/STAT3 signal transduction pathway, reducing the expression and activation of STAT3, increasing the expression of the colon Claudin-1 and restoring the mechanical barrier of the colonic mucosa. At the same time, there was no observation of the TNBS ulcerative colitis with Glycyrrhiza Xiexin soup. Liver and kidney toxicity of model rats. The clinical effect of second part of glycyrrhizin decoction combined with mesalazine on mild and moderate ulcerative colitis: preliminary observation of the efficacy and safety of Glycyrrhizin Combined with mesalazine in the treatment of ulcerative colitis (cold and heat syndrome). Methods: 37 cases of ulcerative colitis in the case of cold and heat disorder The treatment group was randomly divided into 19 cases in the treatment group and 18 cases in the control group. The treatment group took oral licorice Xiexin soup, 1 doses per day, 2 times, and oral mesalazine sustained-release granules, 1g each time, 4 times a day; the control group was treated with mesalazine sustained-release granules, 1g each time, 4 times a day. Two groups were treated for 4 weeks. The curative effect of the two groups was compared to improve the Mayo score standard and TCM syndrome. The scores were evaluated respectively, and the blood routine and liver and kidney function before and after treatment were compared to observe its safety. Results: the treatment group dropped 2 cases and the control group dropped 1 cases. The total effective rate of the treatment group was 76.5%, the control group had a total effective rate of 76.5%, and the two groups had no significant difference (P0.05); the total effective rate of TCM syndrome in the treatment group was 88.3%%, the control group of traditional Chinese Medicine The total effective rate of the syndrome was 70.6%, there was no significant difference between the two groups (P0.05), and the improved Mayo scores in the two groups were significantly lower (P0.01), but there was no significant difference between the two groups (P0.01), and the treatment group was significantly lower than the control group (P0.05). The white blood cell count (WBC) between the two groups before and after treatment (WBC) There was no significant difference in cell count (RBC), hemoglobin concentration (Hb) and platelet count (Plt). There was no significant difference in BUN, Cr, ALT and AST levels between the two groups before and after treatment (P 0.05). Conclusion: the combination of glycyrrhizin Decoction and mesalazine in the treatment of ulcerative colitis can obviously reduce the TCM syndrome score, and the drug use is safe and no obvious blood system is found. Adverse reaction and liver and kidney injury.

【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R259

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