健脾化湿方治疗溃疡性结肠炎脾虚湿蕴证疗效观察及对模型大鼠ERK通路的干预研究

发布时间：2018-11-05 20:18

【摘要】：目的：观察以参苓白术散为基础方加减的健脾化湿方联合美沙拉嗪对轻中度脾虚湿蕴型溃疡性结肠炎的临床效果,并观察健脾化湿方对溃疡性结肠炎模型大鼠结肠组织ERKl/2信号通路的作用,由此探讨其可能的作用机制,为溃疡性结肠炎的中医治疗效果及机理提供依据。方法：临床研究：采用随机对照的方法,将符合轻中度脾虚湿蕴证溃疡性结肠炎标准的患者40例分成治疗组和对照组各20例。两组均口服美沙拉嗪缓释颗粒1克／次,4次/日,治疗组加服健脾化湿方。治疗8周后比较两组患者的近期总疗效、中医证候疗效、肠镜下黏膜病变疗效及治疗前后中医症候积分、疾病活动指数(Sutherland DAI)积分的改善情况。实验研究：采用随机的方法,将45只大鼠分为正常对照组、模型对照组、健脾化湿方组和阳性对照组,除正常对照组外,其余各组采用三硝基苯磺酸诱导法制造大鼠溃疡性结肠炎模型,各组经灌胃给药,健脾化湿方组予健脾化湿方水煎液,阳性对照组予柳氮磺吡啶水溶液,正常对照组及模型对照组予等容积蒸馏水,用药10天后采用HE染色法观察造模大鼠肠黏膜的病理形态,用Westernblot法检测大鼠结肠组织中ERK1/2的表达。结果：临床研究结果示：治疗组和对照组治疗后的中医症候总积分较治疗前均有显著降低(P0.01),治疗后治疗组积分低于对照组(P0.05),中医症候疗效亦优于对照组(P0.05)。治疗前后Sutherland DAI积分均有明显差异(P0.01),治疗后DAI积分治疗组低于对照组(P0.05)；肠镜下黏膜改善情况方面,两组间比较无明显差异(P0.05),治疗组有效率75.00%稍高于对照组有效率50.00%,认为两组效果相当。治疗组近期总疗效总有效率为95.00%高于对照组75.00%,两组间比较无明显差异(P0.05),认为两组效果相当。实验研究结果示：与正常对照组比较,模型对照组有不同程度的充血、水肿、慢性炎细胞浸润,黏膜坏死、溃疡等溃疡性结肠炎活动期组织学病理变化,健脾化湿方组及阳性对照组较模型对照组黏膜层炎细胞浸润有不同程度的减轻。模型对照组大鼠结肠组织ERK1/2较正常对照组表达均明显增多(P0.01)。阳性对照组和健脾化湿方组ERK1的相对表达量与模型对照组比较均有降低(P0.05),在ERK2的表达方面与模型对照组比较均无显著差别(P0.05)。健脾化湿方组在降低ERK1/2表达方面较阳性对照组均无优势(P0.05)。结论：健脾化湿方联合美沙拉嗪能较好的改善轻中度溃疡性结肠炎患者的临床症状及疾病活动指数,短期内对镜下黏膜病变效果不显。作用机制可能是通过抑制ERK信号通路发挥抗炎作用,促进溃疡修复。
[Abstract]:Objective: to observe the clinical effect of Jianpi Huazheng prescription combined with mesalazine on ulcerative colitis of mild and moderate spleen deficiency and dampness accumulation type based on Shenling Baizhu Powder. To observe the effect of Jianpi Huazheng recipe on ERKl/2 signaling pathway in colonic tissue of rats with ulcerative colitis, and to explore its possible mechanism, and to provide the basis for the therapeutic effect and mechanism of ulcerative colitis by traditional Chinese medicine (TCM). Methods: clinical study: 40 patients with ulcerative colitis were divided into treatment group (n = 20) and control group (n = 20). Both groups were orally treated with mesalazine sustained release granules (1 g / d, 4 times per day). The treatment group was treated with Jianpi Huazheng recipe. After 8 weeks of treatment, the general curative effect, TCM syndromes, mucosal lesion under enteroscopy, the score of TCM symptom and the improvement of disease activity index (Sutherland DAI) were compared between the two groups. Experimental study: 45 rats were randomly divided into normal control group, model control group, invigorating spleen and removing dampness prescription group and positive control group, except the normal control group. The rat model of ulcerative colitis was induced by trinitrobenzenesulfonic acid in the other groups. The rats in each group were given intragastric administration, Jianpi Huazheng decoction and salicylazosulfopyridine solution in the positive control group. The normal control group and the model control group were treated with distilled water of equal volume. After 10 days of administration, the pathological morphology of intestinal mucosa of the model rats was observed by HE staining, and the expression of ERK1/2 in the colonic tissue of the rats was detected by Westernblot method. Results: the results of clinical study showed that the total score of TCM symptoms in treatment group and control group was significantly lower than that before treatment (P0.01), and the score of treatment group was lower than that of control group after treatment (P0.05). The curative effect of TCM syndrome was better than that of control group (P0.05). There were significant differences in Sutherland DAI scores before and after treatment (P0.01). After treatment, the DAI scores in the treatment group were lower than those in the control group (P0.05). There was no significant difference between the two groups (P0.05). The effective rate of the treatment group was 75.00% slightly higher than that of the control group 50.00. The total effective rate was 95.00% in the treatment group and 75.00% in the control group. There was no significant difference between the two groups (P0.05). The experimental results showed that compared with the normal control group, the model control group had different degrees of congestion, edema, chronic inflammatory cell infiltration, mucosal necrosis, ulcerative colitis and other ulcerative colitis. Compared with model control group, the infiltration of mucositis cells in Jianpi Huazheng prescription group and positive control group was alleviated to some extent. The expression of ERK1/2 in colonic tissue of model control group was significantly higher than that of normal control group (P0.01). Compared with the model control group, the relative expression of ERK1 in the positive control group and Jianpi Huazheng prescription group was lower than that in the model control group (P0.05), but there was no significant difference in the expression of ERK2 between the positive control group and the model control group (P0.05). There was no advantage in reducing ERK1/2 expression in Jianpi Huazheng Fang group compared with the positive control group (P0.05). Conclusion: Jianpi Huashi prescription combined with mesalazine can improve the clinical symptoms and disease activity index of patients with mild to moderate ulcerative colitis. The mechanism may be the inhibition of ERK signaling pathway to play an anti-inflammatory effect and promote ulcer repair.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R259

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