本文選題：復(fù)發(fā)緩解型多發(fā)性硬化 + 甲潑尼龍��； 參考：《鄭州大學(xué)》2016年博士論文

【摘要】：多發(fā)性硬化(Multiple Sclerosis,MS)是中樞神經(jīng)系統(tǒng)常見的一種自身免疫性疾病,復(fù)發(fā)緩解型多發(fā)性硬化(RRMS)是MS最常見的類型。該病好發(fā)于青壯年勞動力,常反復(fù)發(fā)病,治療成本高,易致殘。近年研究發(fā)現(xiàn),多發(fā)性硬化在國內(nèi)患病率呈上升趨勢。目前,該病的病因和發(fā)病機制至今尚未完全明確。隨著免疫學(xué)研究的進展,新的輔助性T細胞亞群的發(fā)現(xiàn),其與MS發(fā)病關(guān)系的研究也正成為未來研究的重要方向之一,有望在其中發(fā)現(xiàn)新的診斷指標(biāo)或治療靶點。新近研究證實,IL-23的致病作用是由于IL-23誘導(dǎo)CD4+T細胞產(chǎn)生IL-17,IL-17才是MS最為關(guān)鍵的致炎細胞因子。但是這些研究均是在實驗性自身免疫性腦脊髓炎開展,對于MS的研究較少,且對與其密切相關(guān)的IL-17A、IL-23、IL-21、IL-22、IL-6、TGF-β等細胞因子的研究更少。目前國內(nèi)外對IL-17A、IL-23、IL-6等部分細胞因子在MS患者血清中的含量測定,無對比分析腦脊液和血清中細胞因子的變化,也無MS急性復(fù)發(fā)期與緩解期細胞因子水平變化的比較,研究的細胞因子較少,設(shè)計也不完善。我們同時研究急性期RRMS患者大劑量甲潑尼龍沖擊治療1周后和治療1月后血清和或腦脊液中細胞因子含量的變化、細胞因子之間的相關(guān)性、細胞因子與EDSS相關(guān)性、恢復(fù)期與急性復(fù)發(fā)期血清中細胞因子水平的對比研究,研究內(nèi)容全面,設(shè)計合理,為探索MS的發(fā)病機制具有重要意義。炎性細胞因子不僅能誘導(dǎo)MS脫髓鞘病變,與MS非脫髓鞘病灶也密切相關(guān)。當(dāng)MS患者軸索、神經(jīng)元發(fā)生損害后,細胞骨架和軸膜上的Tau蛋白、S100蛋白、14-3-3蛋白,神經(jīng)絲蛋白被釋放到腦脊液中,引起繼發(fā)性免疫反應(yīng)。這在一定程度能反映損害的程度,提示預(yù)后及免疫治療療效。目前國內(nèi)外對ms患者腦脊液和血清中tau蛋白、s100蛋白、14-3-3蛋白或神經(jīng)絲蛋白的部分研究,但研究的結(jié)論并不一致,且未對緩解期ms患者血清中tau蛋白、s100蛋白、14-3-3蛋白或神經(jīng)絲蛋白的動態(tài)觀察,也未探尋其與炎性細胞因子之間的關(guān)系。本研究通過檢測急性復(fù)發(fā)期及緩解期rrms患者血清中tau蛋白、s100蛋白、14-3-3蛋白、神經(jīng)絲蛋白水平,探討甲潑尼龍對其影響tau蛋白、s100蛋白、14-3-3蛋白、神經(jīng)絲蛋白與edss相關(guān)性,探尋炎性細胞因子與ms非脫髓鞘損害相關(guān)的依據(jù)。在治療方面,甲潑尼龍仍是目前我國治療ms急性發(fā)作期的常用藥物。盡管臨床證明甲潑尼龍治療急性復(fù)發(fā)期ms有效,但并不能阻止疾病的復(fù)發(fā),且治療機理不明確。本課題中檢測rrms患者甲潑尼龍治療1周前后、1月后兩個時間段血清和或腦脊液中il-23、il-17a、il-21、il-22、tgf-β、il-6等th17細胞相關(guān)細胞因子水平的變化,以及治療1月后il-23、il-17a、il-21、il-22、tgf-β、il-6等th17細胞相關(guān)細胞因子水平與edss的相關(guān)性,進一步探討甲潑尼龍治療ms的治療機理,為探尋ms發(fā)病機制、明確治療靶點以及探索新的治療靶點有著重要的意義。目的:1、探討rrms患者甲潑尼龍治療1周前后il-23、il-17a水平的變化及其與edss的相關(guān)性;2、探索rrms患者甲潑尼龍治療1月前后血清和腦脊液中il-23、il-17a、il-21、il-22、tgf-β、il-6等th17細胞相關(guān)細胞因子的變化及這些細胞因子之間的相關(guān)性;3、探索rrms患者急性復(fù)發(fā)期與緩解期血清中il-23、il-17a、il-21、il-22、tgf-β、il-6等th17細胞相關(guān)細胞因子的變化及其與rrms再復(fù)發(fā)的關(guān)系;4、探討甲潑尼龍對rrms患者急性期及恢復(fù)期血清中tau蛋白、s100蛋白、14-3-3蛋白、神經(jīng)絲蛋白水平的影響,及其與edss相關(guān)性,與rrms再復(fù)發(fā)的關(guān)系;5、探尋rrms患者血清中il-23、il-17a、il-21、il-22、tgf-β、il-6等th17細胞相關(guān)細胞因子導(dǎo)致ms非脫髓鞘損害的依據(jù)。方法:本研究分三部分:2011年9月到2014年9月鄭州大學(xué)第一附屬醫(yī)院住院確診的rrms患者;發(fā)病48h入院,符合2010年mcdonald診斷標(biāo)準(zhǔn)及中華神經(jīng)科雜志《多發(fā)性硬化診斷和治療中國專家共識(2011版)》診斷標(biāo)準(zhǔn)。共納入rrms患者104例,其中男35例,女69例,平均年齡31.2±11.5歲;病程2個月到9.5年,平均38.2個月;復(fù)發(fā)次數(shù)2-8次,平均3.9次;腦脊液寡克隆區(qū)帶陽性55例(陽性率52.88%),104例患者均有新發(fā)陽性體征/癥狀,頭顱mri均有新發(fā)病灶。第一部分1、設(shè)計路線:根據(jù)擴展殘疾狀況量表(edss)把ms分成三組:ms(a)組(edss:4分),ms(b)組(edss:≥4-6分),ms(c)組(edss:≥6-9分),20例神經(jīng)系統(tǒng)非炎性疾病(nind)患者為對照組,elisa方法檢測nind組和大劑量甲潑尼龍沖擊治療rrms患者1周前后血清中il-23和il-17a水平變化,治療1月后血清和腦脊液中il-23和il-17a水平變化、兩者相關(guān)性以及其與edss的相關(guān)性。2、納入患者情況:確診的rrms患者66例根據(jù)edss分成三組:ms(a)組27例,其中男8例,女19例,平均年齡(35.20±11.71)歲;ms(b)組28例,其中男11例,女17例,平均年齡(33.40±9.18)歲;ms(c)組11例,其中男3例,女8例,平均年齡(36.60±14.50)歲。3、方法及標(biāo)本采集:所有納入患者治療前采肘靜脈血5ml,腰穿抽取腦脊液3ml,立即離心后取上清液分裝于分離管內(nèi),標(biāo)記、凍存待測。rrms組患者給予甲潑尼龍針(1.0givggtqd-3,后0.5givgttqd-4),治療1周時再次采肘靜脈血5ml,同樣方法保存待測。甲潑尼龍沖擊治療1周后口服強的松片60mg/d,漸遞減后1月內(nèi)停服,同時口服保護胃黏膜保護藥,以及補鈣、補鉀藥物治療,口服強的松治療3周(共使用激素治療1月),再次采肘靜脈血5ml,腰穿抽取腦脊液3ml,同樣方法保存待測。神經(jīng)系統(tǒng)非炎癥疾病(nind)患者20例為對照組。第二部分1、設(shè)計路線:檢測rrms患者甲潑尼龍沖擊治療前后血清和腦脊液中il-23、il-17a、il-21、il-22、tgf-β、il-6等th17細胞相關(guān)細胞因子的變化,以及細胞因子之間的相關(guān)性。2、納入患者情況:共納入rrms組患者38例,其中男性13例,女性25例,年齡(31.4±9.5)歲。3、方法及標(biāo)本采集:所有納入患者治療前采肘靜脈血5ml,腰穿抽取腦脊液3ml,立即離心5后取上清液分裝于分離管內(nèi),標(biāo)記、凍存待測。rrms組患者給予甲潑尼龍針(1.0givggtqd-3,后0.5givgttqd-4,后口服強的松片60mg/d,漸遞減后1月內(nèi)停服),同時加用保護胃藥物,補鈣補鉀治療,口服強的松片治療3周后(共使用激素治療1月)再次采肘靜脈血5ml,腰穿抽取腦脊液3ml,同樣方法保存待測。神經(jīng)系統(tǒng)非炎癥疾病(nind)患者20例作為對照組。第三部分:1、設(shè)計方案:參與第一或第二部分研究中的處于緩解期門診隨訪的治療后半年的rrms患者。elisa方法檢測nind組和rrms患者治療前后及緩解期血清中th17細胞相關(guān)細胞因子和tau蛋白,s100蛋白,14-3-3蛋白,神經(jīng)絲蛋白的水平及其與edss相關(guān)性。2、納入患者情況:共納入rrms隨訪患者41例,其中男性14例,女性27例,平均年齡(33.6±10.1)歲,41例患者均無新發(fā)癥狀及體征,復(fù)查頭顱mri均有無發(fā)病灶。納入患者根據(jù)edss分成三組:ms(a)組(edss:4分),ms(b)組(edss:≥4-7分),ms(c)組(edss:≥6-9分),其中ms(a)組17例,其中男5例,女12例,平均年齡(33.12±10.28)歲;ms(b)組18例,其中男7例,女11例,平均年齡(36.27±11.29)歲;ms(c)組6例,其中男2例,女4例,平均年齡(35.44±15.70)歲。3、方法及標(biāo)本采集:所有納入患者治療前采肘靜脈血5ml,立即經(jīng)離心后取上清液分裝于分離管內(nèi),標(biāo)記、凍存待測。結(jié)果:1、甲潑尼龍治療rrms1周及1月后血清中il-23、il-17a的水平進行性下降,腦脊液中il-23、17a水平較治療前亦下降,但兩者仍高于nind組,rrms患者腦脊液中il-17a水平高于血清;2、甲潑尼龍沖擊治療rrms后,患者edss在ms(a)組和ms(b)組均下降,ms(c)組下降不明顯;3、ms組腦脊液中il-17a水平與edss正相關(guān);4、甲潑尼龍治療rrms后血清和腦脊液中il-17a、il-23、il-21、il-22水平較治療前下降,仍較nind組高,tgf-β水平較治療前增高;5、rrms患者治療前血清和腦脊液中tgf-β水平較nind組低,治療后腦脊液中tgf-β水平顯著高于nind組;6、相關(guān)性分析:rrms治療前血清中il-23與il-17a正相關(guān);腦脊液中il-23、il-17a、il-21兩兩正相關(guān);7、rrms恢復(fù)期,血清和腦脊液中il-23、il-17a、il-21、il-22水平仍高于nind組,tgf-β水平低于nind組,提示恢復(fù)期的ms仍存在炎癥反應(yīng);8、rrms患者血清和腦脊液中il-17a與il-23正相關(guān),腦脊液中il-17a、il-23與il-22正相關(guān),提示這3個炎性細胞因子在rrms發(fā)病中存在同向協(xié)調(diào)關(guān)系;9、緩解期rrms患者血清中il-23、il-17a、il-21、il-22水平較急性復(fù)發(fā)期及治療后下降,但仍高于nind組;10、rrms患者甲潑尼龍沖擊治療后血清中s100蛋白水平下降,但恢復(fù)期仍高于nind組;血清中tau蛋白、14-3-3蛋白、神經(jīng)絲蛋白水平無明顯變化;11、rrms患者血清中il-17a、il-23、il-21、il-22、tgf-β與s100蛋白正相關(guān),s100蛋白水平與edss正相關(guān)。結(jié)論:1、甲潑尼龍治療rrms1周和1月后il-23、il-17a水平及edss評分下降,提示il-23、17a與rrms發(fā)病相關(guān);2、甲潑尼龍可以通過降低rrms患者il-23、il-17a水平,發(fā)揮抗炎作用;3、rrms患者il-17a水平與該疾病嚴(yán)重程度相關(guān);4、rrms患者il-23、il-17a、il-21、il-22、tgf-β與rrms發(fā)病相關(guān);5、甲潑尼龍可能通過抑制炎性細胞因子il-23、il-17a、il-21、il-22,上調(diào)tgf-β發(fā)揮抗炎作用;6、恢復(fù)期rrms仍存在高水平的炎性細胞因子,這可能與ms的復(fù)發(fā)相關(guān);7、rrms患者il-17a、il-23與il-22在rrms發(fā)病中存在同向協(xié)調(diào)關(guān)系,提示阻斷il-17a、il-23或il-22的炎性通路,有可能阻斷疾病進展;8、緩解期rrms患者血清中高水平的il-23、il-17a、il-21、il-22,可能與rrms再復(fù)發(fā)相關(guān);9、rrms患者血清中s100蛋白水平恢復(fù)期仍增高,提示rrms患者持續(xù)存在神經(jīng)膠質(zhì)細胞增殖反應(yīng);10、rrms患者血清中s100蛋白水平能預(yù)測rrms患者臨床嚴(yán)重程度;11、il-23、il-17a、il-21、il-22等細胞因子與rrms患者炎性脫髓鞘和非脫髓鞘損害均相關(guān)。
[Abstract]:Multiple sclerosis (Multiple Sclerosis, MS) is a common autoimmune disease in the central nervous system. Relapsed remission multiple sclerosis (RRMS) is the most common type of MS. This disease occurs in young and middle-aged labor, often recurred, with high cost and disability. Recent studies have found that the prevalence of multiple sclerosis is on the rise in the country. At present, the etiology and pathogenesis of the disease have not yet been fully defined. With the progress of immunology research, the discovery of new auxiliary T cell subsets, the study of its relationship with the pathogenesis of MS is also becoming one of the important directions of future research, and a new diagnostic index or therapeutic target is expected to be found in it. Recent studies have confirmed the pathogeny of IL-23. It is because IL-23 induces the production of IL-17 in CD4+T cells. IL-17 is the most critical inflammatory cytokine of MS. However, these studies are carried out in experimental autoimmune encephalomyelitis. There are few studies on MS, and there are fewer studies on the cytokines such as IL-17A, IL-23, IL-21, IL-22, IL-6, TGF- beta, and so on. IL-17A, IL-23, IL-6 and other cytokines were measured in the serum of MS patients. There was no comparison of the changes in cytokines in the cerebrospinal fluid and serum, nor the comparison of the changes in the level of the MS in the acute and remission stage of the cytokine. The cytokine was less in the study and the design was not perfect. At the same time, we studied the large dose of large dose of nail in the acute phase of RRMS patients. The changes in the content of cytokines in serum and cerebrospinal fluid after 1 weeks and after the treatment of prednisolone after January, the correlation between cytokines, the correlation of cytokines and EDSS, the comparison of the level of cytokines in the recovery period and the acute recurrence period of serum, the content of the research is comprehensive and the design is reasonable, which is important to explore the pathogenesis of MS. Inflammatory cytokines can not only induce MS demyelinating lesions, but also be closely related to non demyelinating lesions of MS. When the axons of MS patients are damaged, the Tau protein, S100 protein, 14-3-3 protein, and neurofilament protein on the cytoskeleton and the axial membrane are released into the cerebrospinal fluid and lead to secondary immune responses. This can reflect the damage to a certain extent. Degree, suggesting prognosis and immunotherapy effect. The research on tau protein, S100 protein, 14-3-3 protein or neurofilament protein in cerebrospinal fluid and serum of MS patients at home and abroad is not consistent, and the dynamic observation of tau protein, S100 egg white, 14-3-3 protein or neurofilament protein in serum of MS patients in remission period has not been observed, nor is the dynamic observation of the serum protein, S100 egg white, 14-3-3 protein or neurofilament protein in the patients with MS To explore the relationship between tau protein, S100 protein, 14-3-3 protein and neurofilament protein in the serum of RRMS patients in the acute recurrence and remission period, and to explore the correlation of tau protein, S100 protein, 14-3-3 protein, neurofilament protein and EDSS, and to explore the non - inflammatory cytokines and MS non - In the treatment, methylprednisolone is still a common drug for the treatment of acute attack of MS in our country. Although it is proved that methylprednisolone is effective in the treatment of acute recurrence of MS, but it does not prevent the recurrence of the disease, and the mechanism of treatment is not clear. In this study, the treatment of methylprednisolone for RRMS patients 1 weeks before and after January, after January The changes in the level of IL-23, IL-17A, IL-21, IL-22, tgf- beta, IL-6 and other cytokines in the serum and cerebrospinal fluid of the two time periods, and the correlation of the level of cytokines related to the cytokines of IL-23, IL-17A, IL-21, IL-22, tgf- beta, and IL-6 after January, and further explore the mechanism of the treatment of methylprednisolone. The pathogenesis, the clear target of treatment and the exploration of new therapeutic targets are of great significance. 1, to explore the changes of IL-23, IL-17A level and the correlation with EDSS before and after the treatment of methylprednisolone in RRMS patients. 2, to explore IL-23, IL-17A, IL-21, IL-22, tgf- beta, IL-6, etc. in the serum and cerebrospinal fluid of RRMS patients before and after January Change of cell related cytokines and the correlation between these cytokines. 3, explore the changes in serum IL-23, IL-17A, IL-21, IL-22, tgf- beta, IL-6 and other Th17 cell related cytokines in the serum of RRMS patients at acute recurrence and remission stage, and the relationship with RRMS re recurrence; 4, to explore the tau of methylprednisolone in the acute and convalescent serum of RRMS patients. The effect of protein, S100 protein, 14-3-3 protein, neurofilament level and its correlation with EDSS and the recurrence of RRMS; 5, explore the basis of IL-23, IL-17A, IL-21, IL-22, tgf- beta, IL-6 and other Th17 cell related cytokines in the serum of RRMS patients. Methods: This study was divided into three parts: September 2011 to September 2014 The hospitalized RRMS patients in the First Affiliated Hospital of State University were hospitalized with 48h admission, which met the 2010 McDonald diagnostic criteria and the Chinese Journal of Neurology, the Chinese expert consensus (2011 Edition) for multiple sclerosis diagnosis and treatment. 104 cases of RRMS patients were included, including 35 males and 69 females with an average age of 31.2 + 11.5 years; the course of disease was 2 months to 9.5 years. The average 38.2 months were 2-8 times, an average of 3.9 times, 55 cases of positive cerebrospinal fluid oligoclonal bands (positive rate 52.88%), 104 patients had new positive signs / symptoms, and the head MRI had new lesions. The first part 1, the design route was divided into three groups: ms (a) group (edss:4), MS (b) group (edss: > 4-6) according to the extended disability scale (EDSS). The MS (c) group (edss: > 6-9), 20 cases of non inflammatory disease (nind) of the nervous system as the control group. The ELISA method was used to detect the changes in serum IL-23 and IL-17A levels before and after 1 weeks of RRMS patients in the nind group and the large dose methylprednisolone impact treatment. The changes of IL-23 and IL-17A levels in the serum and cerebrospinal fluid after January were treated and their correlation with EDSS .2 was included in the patients: 66 patients with RRMS were divided into three groups according to EDSS: 27 cases in group MS (a), of which 8 were male and 19 in women (35.20 + 11.71) years, and 28 in group B (b), including 11 men, 17 women, average age (33.40 + 9.18) years and MS (c), including male 3, women,.3, methods and specimen collection: All the patients were taken 5ml of the elbow vein blood before treatment, and the cerebrospinal fluid (3ml) was extracted from the lumbar puncture, then the supernatant was removed in the separation tube immediately after the centrifugation. The patients were treated with methylprednisolone needle (1.0givggtqd-3, 0.5givgttqd-4) after the cryopreservation in.Rrms group. The same method was preserved for 1 weeks after 1 weeks. After taking oral prednisone tablets 60mg/d, gradually decreasing in January, taking oral protection of gastric mucosa, calcium supplementation, potassium supplement, oral administration of prednisone for 3 weeks (using hormone therapy in January), 5ml of elbow vein blood, 3ml of cerebrospinal fluid in the lumbar puncture, and 20 cases of non inflammatory (nind) patients. Control group. Second part 1, design route: test the changes of IL-23, IL-17A, IL-21, IL-22, tgf- beta, IL-6 and other Th17 cell related cytokines in serum and cerebrospinal fluid before and after the treatment of methylprednisolone in RRMS patients, and the correlation between the cytokines and.2, including 38 cases in the RRMS group, including 13 males and 25 women in the RRMS group. Age (31.4 + 9.5) years old.3, method and specimen collection: all the patients were taken 5ml of the elbow vein blood before treatment, and the cerebrospinal fluid (3ml) was extracted from the lumbar puncture, then the supernatant was removed in the separation tube immediately after 5 centrifugation, and the patients in group.Rrms were given the 1.0givggtqd-3, 0.5givgttqd-4, and then oral prednisone 60mg/d, gradually decreasing in January. At the same time, combined with protective stomach medicine, calcium supplement and potassium supplement, 3 weeks after oral administration of prednisone tablets (using hormone therapy in January), the 5ml of the elbow vein was recovered, 3ml of cerebrospinal fluid was extracted from the waist, and the same method was preserved. 20 cases of non inflammatory disease (nind) of the nervous system were used as the control group. The third part: 1, the design was involved in the first or second. In some studies, the.Elisa method of RRMS patients in the remission outpatient follow-up period was used to detect the serum Th17 cell related cytokines and tau protein, the level of S100 protein, 14-3-3 protein, neurofilament protein, and EDSS associated.2 in the serum of nind and RRMS patients before and after the treatment and remission period. The patients were included in the case of RRMS follow up. There were 41 patients, including 14 male and 27 female, average age (33.6 + 10.1) years, 41 patients had no new symptoms and signs, and there were no lesions in the skull MRI. The patients were divided into three groups according to EDSS: ms (a), MS (b) group (edss: > 4-7), MS (c) group (edss: > 6-9), including 17 cases of MS (5, 12, average). Age (33.12 + 10.28) years, MS (b) group 18 cases, including 7 men, 11 women, average age (36.27 + 11.29) years, MS (c) group 6 cases, including 2 men, 4 cases, average age (35.44 + 15.70) years of.3, method and specimen collection: all the patients were collected before the treatment of the elbow vein blood 5ml, immediately after centrifugation and the supernatant in the separation tube, marked, frozen to be measured. Results: 1, the level of IL-23 and IL-17A in serum of rrms1 and January decreased, and the level of il-23,17a in cerebrospinal fluid was also lower than that before treatment, but both of them were still higher than that in group nind. The level of IL-17A in the cerebrospinal fluid of RRMS patients was higher than that in serum; 2, after the methylprednisolone shock treatment RRMS, the patients were all decreased in MS (a) group and MS group. 3, IL-17A level in the cerebrospinal fluid of MS group was positively correlated with EDSS; 4, the level of IL-17A, IL-23, IL-21, IL-22 in the serum and cerebrospinal fluid after RRMS was lower than that before the treatment. The level of tgf- beta was higher than that before the treatment, and the level of tgf- beta was higher than that before the treatment. 5, RRMS patients had lower levels of tgf- beta in the blood and cerebrospinal fluid before treatment and the cerebrospinal fluid after treatment. Gf- beta level was significantly higher than that in nind group; 6, correlation analysis: IL-23 and IL-17A were positive in serum before RRMS treatment; IL-23, IL-17A, IL-21 22 in cerebrospinal fluid were positively correlated; 7, RRMS recovery period, IL-23, IL-17A, IL-21, and IL-21 in serum and cerebrospinal fluid were still higher than those in the group. IL-17A was positively correlated with IL-23 in the patient's serum and cerebrospinal fluid, IL-17A and IL-23 in cerebrospinal fluid were positively correlated with IL-22, suggesting that the 3 inflammatory cytokines have the same coordination relationship in the pathogenesis of RRMS; 9, the serum IL-23, IL-17A, IL-21, IL-22 levels of RRMS patients in the remission stage were lower than those in the acute relapse period and after treatment, but still higher than those in the nind group; 10. The serum S100 protein level decreased after the shock treatment, but the recovery period was still higher than that in the nind group, and there was no significant change in serum tau protein, 14-3-3 protein and neurofilament level. 11, the serum IL-17A, IL-23, IL-21, IL-22, tgf- beta were positively related to S100 protein in the serum of RRMS patients, and the level of S100 protein was positively correlated. Conclusion: 1, methylprednisolone was treated for the week. And after January IL-23, IL-17A level and EDSS score declined, suggesting that il-23,17a was associated with RRMS; 2, methylprednisolone could play an anti-inflammatory effect by reducing IL-23, IL-17A level in patients with RRMS; 3, IL-17A levels in RRMS patients were associated with the severity of the disease; 4 By inhibiting inflammatory cytokines IL-23, IL-17A, IL-21, IL-22, and up regulation of tgf- beta, the anti-inflammatory effect is played. 6, there are still high levels of inflammatory cytokines in the recovery phase RRMS, which may be associated with the recurrence of MS; 7, IL-17A, IL-23 and IL-22 in RRMS patients are in the same direction in the pathogenesis of RRMS. 8, the high level of IL-23, IL-17A, IL-21, IL-22 in the sera of RRMS patients in the remission period may be associated with the recurrence of RRMS; 9, the level of S100 protein in the serum of RRMS patients is still higher, suggesting that the RRMS patients continue to have the proliferation of glial cells; 10, S100 protein levels in the serum of the RRMS patients can predict the clinical manifestation of the RRMS patients. Severity, 11, IL-23, IL-17A, IL-21, IL-22 and other cytokines were correlated with inflammatory demyelination and non demyelination in RRMS patients.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R744.51
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本文編號：1919387