【摘要】：目的：觀察以參苓白術(shù)散為基礎(chǔ)方加減的健脾化濕方聯(lián)合美沙拉嗪對(duì)輕中度脾虛濕蘊(yùn)型潰瘍性結(jié)腸炎的臨床效果,并觀察健脾化濕方對(duì)潰瘍性結(jié)腸炎模型大鼠結(jié)腸組織ERKl/2信號(hào)通路的作用,由此探討其可能的作用機(jī)制,為潰瘍性結(jié)腸炎的中醫(yī)治療效果及機(jī)理提供依據(jù)。方法：臨床研究：采用隨機(jī)對(duì)照的方法,將符合輕中度脾虛濕蘊(yùn)證潰瘍性結(jié)腸炎標(biāo)準(zhǔn)的患者40例分成治療組和對(duì)照組各20例。兩組均口服美沙拉嗪緩釋顆粒1克／次,4次/日,治療組加服健脾化濕方。治療8周后比較兩組患者的近期總療效、中醫(yī)證候療效、腸鏡下黏膜病變療效及治療前后中醫(yī)癥候積分、疾病活動(dòng)指數(shù)(Sutherland DAI)積分的改善情況。實(shí)驗(yàn)研究：采用隨機(jī)的方法,將45只大鼠分為正常對(duì)照組、模型對(duì)照組、健脾化濕方組和陽性對(duì)照組,除正常對(duì)照組外,其余各組采用三硝基苯磺酸誘導(dǎo)法制造大鼠潰瘍性結(jié)腸炎模型,各組經(jīng)灌胃給藥,健脾化濕方組予健脾化濕方水煎液,陽性對(duì)照組予柳氮磺吡啶水溶液,正常對(duì)照組及模型對(duì)照組予等容積蒸餾水,用藥10天后采用HE染色法觀察造模大鼠腸黏膜的病理形態(tài),用Westernblot法檢測大鼠結(jié)腸組織中ERK1/2的表達(dá)。結(jié)果：臨床研究結(jié)果示：治療組和對(duì)照組治療后的中醫(yī)癥候總積分較治療前均有顯著降低(P0.01),治療后治療組積分低于對(duì)照組(P0.05),中醫(yī)癥候療效亦優(yōu)于對(duì)照組(P0.05)。治療前后Sutherland DAI積分均有明顯差異(P0.01),治療后DAI積分治療組低于對(duì)照組(P0.05)；腸鏡下黏膜改善情況方面,兩組間比較無明顯差異(P0.05),治療組有效率75.00%稍高于對(duì)照組有效率50.00%,認(rèn)為兩組效果相當(dāng)。治療組近期總療效總有效率為95.00%高于對(duì)照組75.00%,兩組間比較無明顯差異(P0.05),認(rèn)為兩組效果相當(dāng)。實(shí)驗(yàn)研究結(jié)果示：與正常對(duì)照組比較,模型對(duì)照組有不同程度的充血、水腫、慢性炎細(xì)胞浸潤,黏膜壞死、潰瘍等潰瘍性結(jié)腸炎活動(dòng)期組織學(xué)病理變化,健脾化濕方組及陽性對(duì)照組較模型對(duì)照組黏膜層炎細(xì)胞浸潤有不同程度的減輕。模型對(duì)照組大鼠結(jié)腸組織ERK1/2較正常對(duì)照組表達(dá)均明顯增多(P0.01)。陽性對(duì)照組和健脾化濕方組ERK1的相對(duì)表達(dá)量與模型對(duì)照組比較均有降低(P0.05),在ERK2的表達(dá)方面與模型對(duì)照組比較均無顯著差別(P0.05)。健脾化濕方組在降低ERK1/2表達(dá)方面較陽性對(duì)照組均無優(yōu)勢(P0.05)。結(jié)論：健脾化濕方聯(lián)合美沙拉嗪能較好的改善輕中度潰瘍性結(jié)腸炎患者的臨床癥狀及疾病活動(dòng)指數(shù),短期內(nèi)對(duì)鏡下黏膜病變效果不顯。作用機(jī)制可能是通過抑制ERK信號(hào)通路發(fā)揮抗炎作用,促進(jìn)潰瘍修復(fù)。
[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.
【學(xué)位授予單位】：南京中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R259

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