升阳益胃汤治疗脾胃虚弱证型慢性萎缩性胃炎的临床疗效及血清蛋白质组学的研究

发布时间：2018-10-25 13:20

【摘要】：目的研究升阳益胃汤治疗脾胃虚弱证型慢性萎缩性胃炎(CAG)的临床疗效观察。并应用蛋白质芯片技术寻找CAG差异血清蛋白的表达,探讨中药辨证治疗可能的作用机制。方法临床研究:选取CAG中医辨证分型为脾胃虚弱证患者60例,按随机数字表法分为治疗组及对照组,对照组给予西医临床常规治疗,治疗组在对照组基础上加用升阳益胃汤,治疗3个月后,观察两组临床疗效。实验研究:收集CAG脾胃虚弱证患者治疗前血清10例,给予升阳益胃汤治疗后患者血清10例、健康对照组血清10例,用蛋白质芯片技术对三组血清进行分析,寻找及确定差异蛋白点,采用芯片分析软件提取数据,采用AAH-CYT-G6、AAH-CYT-G7、AAH-CYT-G8、AAH-CYT-G9、AAH-CYT-G10的数据分析软件来进行数据分析,Uniprot及David数据库分析差异蛋白。结果1、临床研究结果表明升阳益胃汤可明显提高临床疗效,与单纯西药对照组有显著性差异(P0.05)。升阳益胃汤治疗组在改善胃镜下征象积分、病理积分方面明显优于西药对照组(P0.05),并改善中医症状积分,减轻中医症状(P0.05)。2、CAG脾胃虚弱证型治疗前与健康对照组差异蛋白鉴定结果:分析得出46个差异蛋白点(P0.05,选取Fold change大于3或小于0.3的信号点,下同),上调的蛋白有33个,下调的蛋白有13个。差异蛋白的生物过程主要涉及到免疫反应、炎症反应、信号转导、趋化作用、凋亡过程的负调节等。3、给予升阳益胃汤治疗后与治疗前相比差异蛋白鉴定结果:分析得出10个差异蛋白点(P0.05),上调的蛋白有4,下调的蛋白有6个。差异蛋白的生物过程主要涉及细胞趋化性、炎症反应、信号转导、细胞信号、免疫反应等。4、结合治疗前与治疗后差异蛋白分析,肿瘤坏死因子受体超家族成员16(NGFR)、金属蛋白酶组织抑制剂因子4(TIMP-4)、趋化因子20(CCL20)由治疗前与健康对照组比较升高转为正常;胰岛素生长因子结合蛋白6(IGFBP-6)、趋化因子4(CCL4)、转化生长因子β2(TGFB2)由治疗前与健康对照组比较降低转为正常。结论1、升阳益胃汤可有效降低胃镜下征象积分、病理积分及中医症状积分。有效的改善临床症状,提高临床疗效。2、CAG脾胃虚弱证型治疗前与健康对照组鉴定得出46个差异蛋白点,其中上调最明显的是CXCL16、TIMP-4、NGFR;下调最明显的是TGFβ2、TNFRSF1A、CCL4。这些差异蛋白可能是其发病相关蛋白,对其进行验证对CAG脾胃虚弱证型的诊断有重要的指导作用。3、升阳益胃汤治疗CAG前后的差异蛋白(NGFR、TIMP-4、CCL20、IGFBP-6、CCL4、TGFB2)可能是中药作用治疗的靶点,改善临床症状、阻止病变进一步发展的相关作用位点,有待进一步验证。
[Abstract]:Objective to study the clinical effect of Shengyang Yiwei decoction on chronic atrophic gastritis (CAG) with deficiency of spleen and stomach. Protein chip technique was used to search for the differential serum protein expression of CAG and to explore the possible mechanism of TCM syndrome differentiation therapy. Methods: 60 patients with deficiency of spleen and stomach were randomly divided into treatment group and control group. The control group was treated with routine western medicine, and the treatment group was treated with Shengyang Yiwei decoction on the basis of the control group. After 3 months of treatment, the clinical effects of the two groups were observed. Experimental study: ten cases of serum of CAG patients with deficiency of spleen and stomach before treatment, 10 cases of serum of patients treated with Shengyang Yiwei decoction and 10 cases of healthy control group were collected. The serum of the three groups was analyzed by protein chip technique. To find and determine the differential protein point, the data were extracted by chip analysis software, the data analysis software of AAH-CYT-G6,AAH-CYT-G7,AAH-CYT-G8,AAH-CYT-G9,AAH-CYT-G10 was used to analyze the data, and the differential protein was analyzed by Uniprot and David database. Results 1. The clinical research results showed that Shengyang Yiwei decoction could significantly improve the clinical efficacy, and there was a significant difference between the control group and the control group (P0.05). 2. The treatment group of Shengyang Yiwei decoction was superior to the western medicine control group in improving the score of signs and pathology under gastroscope (P0.05), and improved the integral of symptoms of traditional Chinese medicine. 2Identification results of differential protein before treatment and healthy control group: 46 differential protein spots (P0.05, Fold change > 3 or less than 0. 3, the same below), 33 proteins upregulated. There are 13 down-regulated proteins. The biological processes of differential proteins are mainly involved in immune response, inflammatory response, signal transduction, chemotaxis. After treatment with Shengyang Yiwei decoction, compared with before treatment, the results of differential protein identification: 10 differential protein points (P0.05), 4 up-regulated proteins and 6 down-regulated proteins. The biological processes of differential proteins are mainly involved in chemotaxis, inflammation, signal transduction, cell signal, immune response, etc. Tumor necrosis factor receptor superfamily member 16 (NGFR), tissue inhibitor of metalloproteinase 4 (TIMP-4) and chemokine 20 (CCL20) increased from normal to normal compared with control group. The levels of insulin growth factor binding protein 6 (IGFBP-6), chemokine 4 (CCL4) and transforming growth factor 尾 2 (TGFB2) were decreased from normal to normal after treatment. Conclusion 1. Shengyang Yiwei decoction can effectively reduce the symptom integral, pathological integral and TCM symptom integral under gastroscopy. 2before treatment, 46 differential protein points were identified in CAG spleen and stomach deficiency syndrome, and the most obvious up-regulation was the down-regulation of TGF 尾 _ 2 TNFRSF _ 1A and CCL4, and the most obvious up-regulation was that of TGF 尾 _ 2 TNFRSF _ (1) A and CCL4. These differential proteins may be its pathogenetic related proteins, which have important guiding role in the diagnosis of spleen and stomach deficiency syndrome type of CAG. 3. The differential protein (NGFR,TIMP-4,CCL20,IGFBP-6,CCL4,TGFB2) before and after treatment with Shengyang Yiwei decoction may be the target of TCM action therapy. The related action sites to improve the clinical symptoms and prevent the further development of the disease need to be further verified.
【学位授予单位】：锦州医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R259

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