本文選題：強(qiáng)直性脊柱炎 + 選擇性�。� 參考：《鄭州大學(xué)》2016年碩士論文

【摘要】：背景:強(qiáng)直性脊柱炎(Ankylosing Spondylitis,AS)是一種常見的慢性、炎癥性、進(jìn)展性的風(fēng)濕性疾病,屬于脊柱關(guān)節(jié)炎的典型類型。以脊柱和骶髂關(guān)節(jié)受累最為常見,部分患者也可出現(xiàn)外周關(guān)節(jié)炎及關(guān)節(jié)外的表現(xiàn),如髖、膝、肩關(guān)節(jié)、心、肺、腎等;AS特征性的表現(xiàn)是慢性炎癥、新骨形成、脊柱關(guān)節(jié)強(qiáng)直,如竹節(jié)樣變,髖關(guān)節(jié)的強(qiáng)直等,嚴(yán)重影響患者的正常活動(dòng),引起生活質(zhì)量下降。非甾體類抗炎藥(non-steroidal anti-inflammatory drugs,NSAIDs)是治療AS的一線用藥,其不僅具有抗炎止痛、改善功能的作用,同時(shí)有研究發(fā)現(xiàn)持續(xù)應(yīng)用塞來昔布可以延緩脊柱影像學(xué)進(jìn)展。艾瑞昔布是中國原研的少有的藥物之一,目前缺乏其在AS方面的相關(guān)研究,那么它是否可以同塞來昔布一樣具有同樣的療效呢?AS骨贅形成是最主要的致殘?jiān)?尋求影響AS骨贅形成的因素具有重要的臨床意義。骨形態(tài)發(fā)生蛋白(bone morphogenetic protein,BMP)是參與骨形成的最重要的活性物質(zhì),誘導(dǎo)骨形成、促進(jìn)成骨細(xì)胞分化,并能夠誘導(dǎo)血管、間充質(zhì)細(xì)胞以及纖維細(xì)胞等轉(zhuǎn)化為不可逆的骨系細(xì)胞。AS骨化的發(fā)生主要是軟骨內(nèi)成骨,而血管內(nèi)皮生長因子對于血管的生成以及軟骨內(nèi)骨化均具有重要的作用,同時(shí)也可能參與了AS新骨形成。AS的炎癥過程與環(huán)氧化酶病理性的表達(dá)密切相關(guān),非甾體類抗炎藥作為AS的一線用藥,主要通過抑制環(huán)氧化酶的活性,減少前列腺素的合成,而發(fā)揮抗炎和改善病情的作用。已有研究發(fā)現(xiàn)環(huán)氧化酶可通過影響VEGF、BMP的表達(dá)參與血管內(nèi)皮的損傷、腫瘤的發(fā)生發(fā)展以及骨轉(zhuǎn)移等;COX-2選擇性抑制劑塞來昔布可以緩解AS患者脊柱影像學(xué)的進(jìn)展,但其具體作用機(jī)制尚不是十分清楚。血清VEGF和BMP-2的水平是否與骶髂關(guān)節(jié)影像學(xué)進(jìn)展相關(guān)?并且選擇性COX-2抑制劑是否對VEGF和BMP-2的表達(dá)有影響呢?因此,我們進(jìn)行了此次研究。目的:1.評價(jià)COX-2選擇性抑制劑對于AS患者的療效,并比較艾瑞昔布和塞來昔布間療效差異。2.評價(jià)COX-2選擇性抑制劑對AS患者影像學(xué)評分的影響。3.觀察COX-2選擇性抑制劑對AS患者血清VEGF、BMP-2水平的影響,以及血清VEGF、BMP-2與影像學(xué)的關(guān)系。方法:選取2014年10月至2015年10月于鄭州大學(xué)第一附屬醫(yī)院風(fēng)濕免疫科門診就診的AS患者120例,要求其均符合一定的納入排除標(biāo)準(zhǔn)。將入組患者隨機(jī)分組,分別給予COX-2選擇性抑制劑艾瑞昔布或塞來昔布200mg,每天兩次口服。治療前記錄患者的基本特征(年齡、性別、病程、入組前治療情況),分別記錄治療前、治療后4周、治療后12周時(shí)患者的實(shí)驗(yàn)室指標(biāo)(血尿常規(guī)、肝腎功能、ESR、CRP)、病情活動(dòng)度(BASDAI評分)以及功能評價(jià)指標(biāo)(BASFI評分、患者總體評估、耳壁距、腰椎側(cè)彎度、踝間距、Schober試驗(yàn)、前指地距)的情況,以及治療前和治療后12周的骶髂關(guān)節(jié)SPARCC評分,并通過酶聯(lián)免疫吸附試驗(yàn)(ELISA)的方法檢測治療前、治療后12周時(shí)血清VEGF、BMP-2的水平。結(jié)果:1.本研究共納入120例AS患者,完成12周隨訪116例,其中包括艾瑞昔布組57例,塞來昔布組59例。兩組在性別、年齡上無顯著差異。治療后4周以及12周,ESR、BASDAI評分、患者總體評估、踝間距、Schober和前指地距的變化情況差異均具有統(tǒng)計(jì)學(xué)意義(P0.05),而CRP在治療后4周其變化情況無統(tǒng)計(jì)學(xué)意義(P0.05),在治療后12周變化情況差異有統(tǒng)計(jì)學(xué)意義(P0.05)。艾瑞昔布與塞來昔布組進(jìn)行比較,CRP在治療后4周時(shí)變化情況差異具有統(tǒng)計(jì)學(xué)意義(P0.05),其余各項(xiàng)指標(biāo)在兩個(gè)時(shí)間點(diǎn)的變化情況差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。重復(fù)測量方差分析,結(jié)果顯示ESR、CRP、BASDAI、患者總體評估、踝間距、前指地距在時(shí)間主效應(yīng)上差異具有統(tǒng)計(jì)學(xué)意義(P0.05),可以認(rèn)為兩組以上指標(biāo)在各個(gè)時(shí)間點(diǎn)上的總體均數(shù)不全相同,其中ESR、BASDAI、患者總體評估、前指地距均數(shù)隨治療時(shí)間增長而下降,踝間距則呈增長趨勢;而CRP結(jié)果顯示時(shí)間主效應(yīng)與處理主效應(yīng)對其均值變化的差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。2.經(jīng)選擇性COX-2抑制劑治療后12周,骶髂關(guān)節(jié)SPARCC評分均較前下降,差異具有統(tǒng)計(jì)學(xué)意義(11.99±12.76 vs 7.11±9.7,P=0.000);艾瑞昔布與塞來昔布組進(jìn)行比較,SPARCC評分變化情況差異無統(tǒng)計(jì)學(xué)意義(-4.01±8.88 vs-5.71±10.6,P0.05)。Spearman相關(guān)性分析結(jié)果顯示SPARCC評分與Schobber試驗(yàn)、腰椎活動(dòng)度、ESR呈正相關(guān)(Schober試驗(yàn):r=0.283,P=0.006;腰椎側(cè)彎度左側(cè):r=0.315,P=0.002,右側(cè):r=0.357,P=0.000;ESR:r=0.236,P=0.022),與年齡、病程、耳壁距呈負(fù)相關(guān)(年齡r=-0.388,P=0.000;病程r=-0.335,P=0.001;耳壁距r=-0.245,P=0.018),與CRP、BASDAI、BASFI、患者總體評估等無明顯相關(guān)性(P0.05)。3.經(jīng)選擇性COX-2抑制劑治療后12周,血清VEGF水平較治療前降低,差異具有統(tǒng)計(jì)學(xué)意義(VEGF:243.82±19.09 vs 191.29±12.09pg/ml,P=0.002);血清BMP-2水平較治療前降低,但差異無統(tǒng)計(jì)學(xué)意義(BMP-2:2.29±1.09 vs 2.23±1.19 pg/ml,P=0.421)。Spearman相關(guān)性分析結(jié)果顯示血清VEGF與BMP-2呈正相關(guān)(P0.05),血清VEGF水平與PLT、ESR、CRP、BASFI、耳壁距、前指地距呈正相關(guān)(P0.05),與HGB、腰椎側(cè)彎度、Schober試驗(yàn)、踝間距呈負(fù)相關(guān);血清BMP-2水平與ESR呈正相關(guān)(P0.05),與腰椎側(cè)彎度呈負(fù)相關(guān)(P0.05)。結(jié)論:1選擇性COX-2抑制劑對AS具有較好的療效并且可以減少骶髂關(guān)節(jié)的炎癥;并且艾瑞昔布與塞來昔布療效相當(dāng)。2血清VEGF可以作為評價(jià)AS病情活動(dòng)的指標(biāo),但非影像學(xué)進(jìn)展的標(biāo)志物,選擇性COX-2抑制劑可以降低血清VEGF的水平。而BMP-2對AS的影響需要進(jìn)一步研究。
[Abstract]:Background: Ankylosing Spondylitis (AS) is a common chronic, inflammatory, progressive rheumatic disease, which belongs to the typical type of spinal arthritis. It is the most common type of spinal and sacroiliac joint involvement. Some patients can also appear peripheral arthritis and out of joint manifestations, such as hip, knee, shoulder joint, heart, lung, and kidney, and so on; AS The manifestations are chronic inflammation, new bone formation and ankylosis of the spine, such as slub like change and the ankylosis of the hip joint, which seriously affect the normal activities of the patients and cause a decline in the quality of life. Non steroidal anti-inflammatory drugs (non-steroidal anti-inflammatory drugs, NSAIDs) are the first-line drugs for the treatment of AS, which not only have anti-inflammatory analgesic pain and improve function. At the same time, it has been found that continuous use of celecoxib can delay the progression of spinal imaging. Alimioxib is one of the most rare drugs in China and is lacking in AS related studies. Is it as effective as celecoxib? AS osteophyte formation is the main cause of disability and search for shadow The factors affecting the formation of AS osteophyte have important clinical significance. Bone morphogenetic protein (BMP) is the most important active substance involved in bone formation, induces bone formation, promotes osteoblast differentiation, and can induce blood vessels, mesenchymal cells and fibrous cells to convert to irreversible ossification of irreversible bone cell cells. The pathogenesis is mainly endochondral osteogenesis, and vascular endothelial growth factor plays an important role in angiogenesis and endochondral ossification, and it may also be involved in the inflammatory process of the AS new bone formation of.AS and the pathological expression of cyclooxygenase. Non steroidal anti-inflammatory drugs are used as the front-line use of AS, mainly by inhibiting the epoxidation of cyclooxygenase. Enzyme activity, which reduces the synthesis of prostaglandins, plays the role of anti-inflammatory and improving the disease. It has been found that cyclooxygenase can be involved in vascular endothelial damage, tumor development and bone metastasis by influencing the expression of VEGF, BMP expression, and COX-2 Selective Inhibitor Celecoxib can relieve the progress of spinal imaging in AS patients, but it can be used to reduce the progress of spinal imaging. The specific mechanism is not yet very clear. Is the level of serum VEGF and BMP-2 related to the imaging progress of the sacroiliac joint? And is selective COX-2 inhibitors affect the expression of VEGF and BMP-2? Therefore, we conducted this study. Objective: 1. to evaluate the efficacy of COX-2 selective inhibitors in AS patients and to compare Ai Ruixi. Effect difference between cloth and celecoxib.2. evaluation of the effect of COX-2 selective inhibitors on the imaging score of AS patients.3. observation of the effect of COX-2 selective inhibitors on serum VEGF, BMP-2 level in AS patients and the relationship between serum VEGF, BMP-2 and imaging. Methods: from October 2014 to October 2015 at the First Affiliated Hospital of Zhengzhou University rheumatism 120 patients with AS in the Department of immunology were asked to conform to a certain inclusion criteria. The patients were divided into groups randomly and were given COX-2 selective inhibitors alisoxib or celecoxib 200mg each day for oral administration. The basic characteristics of the patients were recorded before treatment (age, sex, course of disease, before group treatment), and the treatment was recorded respectively. 4 weeks after treatment, 4 weeks after treatment, the patient's laboratory indexes (hematuria routine, liver and kidney function, ESR, CRP), disease activity (BASDAI score) and functional evaluation index (BASFI score, overall assessment of the patient, ear wall distance, lumbar lateral curvature, ankle distance, Schober test, anterior finger distance), and sacroiliac before and after treatment 12 weeks after treatment, and 12 weeks after treatment and after treatment, and the sacroiliac clearance before and after treatment. SPARCC scores and serum VEGF and BMP-2 levels at 12 weeks after treatment were detected by enzyme linked immunosorbent assay (ELISA). Results: 1. this study included 120 cases of AS patients and 116 cases were followed up for 12 weeks, including 57 of the elioxib group and 59 cases in the celecoxib group. The two groups had no significant difference in sex and age for 4 weeks after the treatment. And 12 weeks, ESR, BASDAI score, the overall assessment of patients, the gap between the ankle, Schober and the distance of the anterior finger were statistically significant (P0.05), but there was no significant difference in the change of CRP at the 4 week after the treatment (P0.05). The difference between the 12 weeks after the treatment was statistically significant (P0.05). The variation of CRP at 4 weeks after treatment was statistically significant (P0.05), and the changes of the other indexes at two time points were not statistically significant (P0.05). Repeated measurements of variance analysis showed that the overall assessment of ESR, CRP, and BASDAI, the difference between the ankle distance and the anterior finger distance was statistically significant (P 0.05), it can be considered that the total average number of all the two sets of indicators at all time points is not the same, in which ESR, BASDAI, the overall assessment of the patients, the average number of the anterior finger distance decreases with the growth of the treatment time, and the distance between the ankle is increasing, and the CRP result shows that the difference between the time main effect and the principal effect on the mean change of the mean time is statistically significant. The SPARCC score of sacroiliac joint was decreased at 12 weeks after the treatment of selective COX-2 inhibitor, and the difference was statistically significant (11.99 + 12.76 vs 7.11 + 9.7, P=0.000). Compared with the celecoxib group, the difference of the SPARCC score was not statistically significant (-4.01 + 8.88 vs-5.71 + 10.6, P0.05).Spearman correlation The results showed that the SPARCC score was positively correlated with the Schobber test, the lumbar activity and the ESR (Schober test: r=0.283, P=0.006; the left side of the lumbar spine: r=0.315, P=0.002, and the right: r=0.357, P=0.000; ESR:r=0.236, P=0.022). 018), there was no significant correlation with CRP, BASDAI, BASFI, and the overall assessment of patients (P0.05). The serum VEGF level was lower than before the treatment (VEGF:243.82 + 19.09 vs 191.29 + 12.09pg/ml, P=0.002) after 12 weeks after the treatment of selective COX-2 inhibitors (VEGF:243.82 + 19.09 vs 191.29 + 12.09pg/ml, P=0.002), but there was no significant difference in the level of serum BMP-2. .29 + 1.09 vs 2.23 + 1.19 pg/ml, P=0.421).Spearman correlation analysis showed that serum VEGF and BMP-2 had positive correlation (P0.05). The level of serum VEGF was positively correlated with PLT, ESR, CRP, ear wall distance, and the distance between the anterior finger, and the lateral curvature of the lumbar vertebrae. The side curvature of the vertebral side is negatively correlated (P0.05). Conclusion: 1 selective COX-2 inhibitors have a good effect on AS and can reduce the inflammation of the sacroiliac joint; and the effect of alisoxib and celecoxib is equivalent to.2 serum VEGF as a marker for evaluating the activity of the AS disease, but the selective COX-2 inhibitor can be reduced. The level of serum VEGF, while the effect of BMP-2 on AS needs further study.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R593.23

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2 南京軍區(qū)福州總醫(yī)院內(nèi)分泌科 馮修高 整理 吳志 張文明;肺炎衣原體可引發(fā)強(qiáng)直性脊柱炎[N];健康報(bào);2013年

3 中華醫(yī)學(xué)會(huì)風(fēng)濕病學(xué)分會(huì)候任主任委員 北京協(xié)和醫(yī)院風(fēng)濕科主任醫(yī)師 曾小峰;強(qiáng)直性脊柱炎能被有效控制[N];光明日報(bào);2013年

4 本報(bào)記者 姜晨怡;強(qiáng)直性脊柱炎 易被誤診的“不死癌癥”[N];科技日報(bào);2013年

5 本報(bào)記者 熊昌彪;治療強(qiáng)直性脊柱炎要走出兩個(gè)誤區(qū)[N];中國醫(yī)藥報(bào);2013年

6 馮興華;中醫(yī)治療強(qiáng)直性脊柱炎[N];健康報(bào);2003年

7 ;強(qiáng)直性脊柱炎及早治療是關(guān)鍵[N];上�？萍紙�(bào);2002年

8 石蘭;強(qiáng)直性脊柱炎的康復(fù)護(hù)理[N];醫(yī)藥養(yǎng)生保健報(bào);2005年

9 劉秀鳳;強(qiáng)直性脊柱炎的康復(fù)運(yùn)動(dòng)[N];醫(yī)藥養(yǎng)生保健報(bào);2005年

10 周武;強(qiáng)直性脊柱炎為何易誤診？[N];浙江日報(bào);2003年

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2 趙英華;磁共振成像對強(qiáng)直性脊柱炎骶髂關(guān)節(jié)炎活動(dòng)性的檢測[D];南方醫(yī)科大學(xué);2015年

3 劉軍;ANO6,HAPLN1,EDIL3在中國漢族人群中與強(qiáng)直性脊柱炎的易感性及嚴(yán)重程度的相關(guān)性的研究[D];天津醫(yī)科大學(xué);2015年

4 陳猛;調(diào)節(jié)性B細(xì)胞在強(qiáng)直性脊柱炎（Ankylosing spondylitis AS）患者中的分布及功能[D];山東大學(xué);2016年

5 周穎燕;補(bǔ)腎強(qiáng)督法治療強(qiáng)直性脊柱炎的療效及抗骨化作用初探[D];廣州中醫(yī)藥大學(xué);2016年

6 李岱鶴;強(qiáng)直性脊柱炎患者局部與全身基質(zhì)Gla蛋白（MGP）表達(dá)下降與影像學(xué)進(jìn)展的聯(lián)系[D];重慶醫(yī)科大學(xué);2015年

7 冉博;HRH4基因多態(tài)性與強(qiáng)直性脊柱炎易感性相關(guān)研究[D];中國人民解放軍醫(yī)學(xué)院;2016年

8 李大河;強(qiáng)直性脊柱炎韌帶組織比較蛋白質(zhì)組學(xué)研究及膜聯(lián)蛋白A2功能驗(yàn)證[D];第二軍醫(yī)大學(xué);2016年

9 張虎;強(qiáng)直性脊柱炎關(guān)節(jié)滑膜高表達(dá)碳酸酐酶1[D];山東大學(xué);2011年

10 朱洪民;強(qiáng)直性脊柱炎早期診斷的臨床研究[D];南方醫(yī)科大學(xué);2011年

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2 王剛;強(qiáng)直性脊柱炎的診斷與治療相關(guān)研究[D];中國人民解放軍醫(yī)學(xué)院;2015年

3 楊帆;TNF-α拮抗劑與傳統(tǒng)藥物相比對全髖關(guān)節(jié)置換術(shù)后強(qiáng)直性脊柱炎患者關(guān)節(jié)功能影響的研究[D];中國人民解放軍醫(yī)學(xué)院;2015年

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5 胡艷婷;強(qiáng)直性脊柱炎患者主觀幸福感現(xiàn)狀及影響因素分析[D];安徽醫(yī)科大學(xué);2015年

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7 劉麗;強(qiáng)直性脊柱炎（AS）患者外周血單個(gè)核細(xì)胞中miRNAs的表達(dá)與血清細(xì)胞因子相關(guān)性研究[D];安徽醫(yī)科大學(xué);2015年

8 徐立偉;祛瘀舒督顆粒治療強(qiáng)直性脊柱炎臨床觀察[D];中國中醫(yī)科學(xué)院;2015年

9 李亭;活動(dòng)期強(qiáng)直性脊柱炎骶髂關(guān)節(jié)的磁共振擴(kuò)散加權(quán)成像研究[D];山西醫(yī)科大學(xué);2015年

10 焦蕊蕊;實(shí)時(shí)超聲彈性成像對強(qiáng)直性脊柱炎患者跟腱損傷的評估價(jià)值[D];山西醫(yī)科大學(xué);2015年

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