【摘要】：目的研究升陽益胃湯治療脾胃虛弱證型慢性萎縮性胃炎(CAG)的臨床療效觀察。并應用蛋白質芯片技術尋找CAG差異血清蛋白的表達,探討中藥辨證治療可能的作用機制。方法臨床研究:選取CAG中醫(yī)辨證分型為脾胃虛弱證患者60例,按隨機數(shù)字表法分為治療組及對照組,對照組給予西醫(yī)臨床常規(guī)治療,治療組在對照組基礎上加用升陽益胃湯,治療3個月后,觀察兩組臨床療效。實驗研究:收集CAG脾胃虛弱證患者治療前血清10例,給予升陽益胃湯治療后患者血清10例、健康對照組血清10例,用蛋白質芯片技術對三組血清進行分析,尋找及確定差異蛋白點,采用芯片分析軟件提取數(shù)據(jù),采用AAH-CYT-G6、AAH-CYT-G7、AAH-CYT-G8、AAH-CYT-G9、AAH-CYT-G10的數(shù)據(jù)分析軟件來進行數(shù)據(jù)分析,Uniprot及David數(shù)據(jù)庫分析差異蛋白。結果1、臨床研究結果表明升陽益胃湯可明顯提高臨床療效,與單純西藥對照組有顯著性差異(P0.05)。升陽益胃湯治療組在改善胃鏡下征象積分、病理積分方面明顯優(yōu)于西藥對照組(P0.05),并改善中醫(yī)癥狀積分,減輕中醫(yī)癥狀(P0.05)。2、CAG脾胃虛弱證型治療前與健康對照組差異蛋白鑒定結果:分析得出46個差異蛋白點(P0.05,選取Fold change大于3或小于0.3的信號點,下同),上調的蛋白有33個,下調的蛋白有13個。差異蛋白的生物過程主要涉及到免疫反應、炎癥反應、信號轉導、趨化作用、凋亡過程的負調節(jié)等。3、給予升陽益胃湯治療后與治療前相比差異蛋白鑒定結果:分析得出10個差異蛋白點(P0.05),上調的蛋白有4,下調的蛋白有6個。差異蛋白的生物過程主要涉及細胞趨化性、炎癥反應、信號轉導、細胞信號、免疫反應等。4、結合治療前與治療后差異蛋白分析,腫瘤壞死因子受體超家族成員16(NGFR)、金屬蛋白酶組織抑制劑因子4(TIMP-4)、趨化因子20(CCL20)由治療前與健康對照組比較升高轉為正常;胰島素生長因子結合蛋白6(IGFBP-6)、趨化因子4(CCL4)、轉化生長因子β2(TGFB2)由治療前與健康對照組比較降低轉為正常。結論1、升陽益胃湯可有效降低胃鏡下征象積分、病理積分及中醫(yī)癥狀積分。有效的改善臨床癥狀,提高臨床療效。2、CAG脾胃虛弱證型治療前與健康對照組鑒定得出46個差異蛋白點,其中上調最明顯的是CXCL16、TIMP-4、NGFR;下調最明顯的是TGFβ2、TNFRSF1A、CCL4。這些差異蛋白可能是其發(fā)病相關蛋白,對其進行驗證對CAG脾胃虛弱證型的診斷有重要的指導作用。3、升陽益胃湯治療CAG前后的差異蛋白(NGFR、TIMP-4、CCL20、IGFBP-6、CCL4、TGFB2)可能是中藥作用治療的靶點,改善臨床癥狀、阻止病變進一步發(fā)展的相關作用位點,有待進一步驗證。
[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.
【學位授予單位】：錦州醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R259

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