甘草泻心汤治疗溃疡性结肠炎的作用机制研究及临床疗效观察

发布时间：2018-05-03 16:25

本文选题：溃疡性结肠炎 + 甘草泻心汤　；参考：《南京中医药大学》2017年博士论文

【摘要】：第一部分甘草泻心汤对TNBS结肠炎模型大鼠的作用机制研究目的:观察甘草泻心汤对溃疡性结肠炎模型大鼠的疗效;并研究甘草泻心汤对溃疡性结肠炎模型大鼠IL-6/STAT3信号通路中相关分子的调节作用以及对Claudin-1的调节作用。以期揭示其治疗溃疡性结肠炎的作用机制及安全效应。方法:将60只SD大鼠随机分为空白组、模型组、美沙拉嗪组(5-ASA组)、甘草泻心汤低剂量组(GCXX-L组)、甘草泻心汤中剂量组(GCXX-M组)和甘草泻心汤高剂量组(GCXX-H组)6组,每组10只。除空白组外均以TNBS造模,造模后空白组和模型组以生理盐水灌胃,5-ASA组和甘草泻心汤各剂量组分别以美沙拉嗪、甘草泻心汤低、中、高剂量灌胃,治疗14天,治疗过程中观察大鼠的一般情况,记录排便情况及体重变化;14天后从鼠尾静脉取血,检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素氮(BUN)、肌酐(Cr)含量,并以ELISA法检测外周血中IL-6表达水平;并对大鼠肝、肾、结肠进行大体观察及显微镜下病理观察;以免疫组化分析各组大鼠结肠组织IL-6、Claudin-1、STAT3及磷酸化STAT3(P-STAT3)的表达;以Real-time PCR法检测各组结肠组织IL-6 mRNA、Claudin-1 mRNA、STAT3 mRNA 的表达。结果:与空白组比较,造模后大鼠出现粪便污染肛周皮毛及体重下降现象(P0.01),血清AST含量明显升高(P0.01),而ALT、BUN、Cr无明显变化(P0.05);外周血IL-6表达明显升高(P0.01);结肠大体评分和组织病理评分明显增加(P0.01);结肠组织IL-6、STAT3和P-STAT3蛋白表达明显增高(P0.01),而Claudin-1蛋白表达明显降低(P0.01);IL-6 和 STAT3 mRNA 表达明显增高(P0.01),Claudin-1 mRNA 表达明显降低(P0.01)。与模型组比较,经美沙拉嗪及甘草泻心汤治疗后,大鼠粪便污染肛周皮毛时间均有所缩短(P0.01)、体重有所增加(P0.01);除5-ASAZ组外,血清AST含量有所降低(P0.01);外周血IL-6表达明显下降(P0.05);除GCXX-L组外结肠大体评分和组织病理评分有所降低(P0.05);结肠组织IL-6、STAT3和P-STAT3蛋白表达有所降低(P0.05),Claudin-1蛋白表达有所增高(P0.05);IL-6和STAT3 mRNA的表达有所降低(P0.01),Claudin-1 mRNA的表达有所增高(P0.01)。结论:甘草泻心汤能够明显改善TNBS溃疡性结肠炎大鼠的一般症状,减轻结肠组织损伤及组织结构的改变,且中剂量即可达到较好效果。甘草泻心汤作用机制可能与其降低组织及外周血IL-6表达,抑制IL-6/STAT3信号转导通路,降低STAT3表达与活化,增加结肠Claudin-1表达,恢复结肠黏膜机械屏障等有关。同时本实验未观察到甘草泻心汤对TNBS溃疡性结肠炎模型大鼠的肝肾毒性。第二部分甘草泻心汤联合美沙拉嗪对轻中度溃疡性结肠炎的临床疗效观察目的:初步观察甘草泻心汤联合美沙拉嗪治疗溃疡性结肠炎(寒热错杂证)的疗效和安全性。方法:将证属寒热错杂的溃疡性结肠炎患者37例,随机分为治疗组19例、对照组18例。治疗组口服甘草泻心汤,每日1剂,分2次服用,同时口服美沙拉嗪缓释颗粒,每次1g,每日4次;对照组口服美沙拉嗪缓释颗粒,每次1g,每日4次。两组均治疗4周。比较两组的疗效,以改良Mayo评分标准及中医证候积分分别进行评价,并比较治疗前后血常规及肝肾功能,以观察其安全性。结果:治疗组脱落2例、对照组脱落1例患者。治疗组总有效率76.5%,对照组总有效率76.5%,两组疗效无显著性差异(P0.05);治疗组中医证候疗效总有效率88.3%%,对照组中医证候疗效总有效率70.6%,两组间无显著性差异(P0.05);治疗后两组改良Mayo评分均显著降低(P0.01),但两组间无显著差异(P0.05);治疗后两组中医证候评分均显著降低(P0.01),且治疗组明显低于对照组(P0.05)。治疗前后两组间白细胞计数(WBC)、红细胞计数(RBC)、血红蛋白浓度(Hb)、血小板计数(Plt)均无显著差异(P均0.05)。治疗前后两组间BUN、Cr、ALT、AST水平均无显著差异(P均0.05)。结论:甘草泻心汤联合美沙拉嗪用于治疗溃疡性结肠炎可明显降低中医证候积分,且用药安全,未见明显血液系统不良反应及肝肾损伤。
[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.

【学位授予单位】：南京中医药大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R259

【相似文献】