本文關(guān)鍵詞： CXCL10 IL-33 腎綜合征出血熱 漢灘病毒 內(nèi)皮細(xì)胞 細(xì)胞因子風(fēng)暴　出處：《第四軍醫(yī)大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：漢灘病毒(Hantaan virus,HTNV)感染在人類可引起的嚴(yán)重的死亡率高達(dá)2%-10%的腎綜合征出血熱(hemorrhagic fever with renal syndrome,HFRS),全球每年約有100,000病例,其中90%以上發(fā)生在我國(guó),陜西省為HFRS的高發(fā)區(qū)。HFRS患者的主要臨床表現(xiàn)為發(fā)熱、出血、血小板數(shù)量下降和急性腎功能不全。由于HTNV感染在宿主嚙齒類動(dòng)物上無(wú)疾病表現(xiàn),因缺乏合適的動(dòng)物模型,目前對(duì)于HTNV感染導(dǎo)致HFRS的致病機(jī)制尚不清楚。血小板功能障礙和毛細(xì)血管內(nèi)皮細(xì)胞損傷為HFRS患者的主要病理表現(xiàn),有研究表明,過(guò)度活化的免疫應(yīng)答和炎癥反應(yīng)引起的“細(xì)胞因子風(fēng)暴”可能是導(dǎo)致HFRS致病的機(jī)理之一。但目前對(duì)于HTNV感染通過(guò)怎樣的機(jī)制引起細(xì)胞因子產(chǎn)生以及如何誘發(fā)“細(xì)胞因子風(fēng)暴”尚不清楚。在我們前期工作中,用Luminex技術(shù)檢測(cè)了HFRS患者血清中多種細(xì)胞因子的表達(dá),其中CXCL10是表達(dá)最高的一種細(xì)胞因子。CXCL10又稱為IFN-γ誘導(dǎo)蛋白10,是CXC趨化因子家族的成員,主要由內(nèi)皮細(xì)胞,上皮細(xì)胞和角質(zhì)形成細(xì)胞分泌產(chǎn)生。CXCL10與受體CXCR3結(jié)合后,可趨化淋巴細(xì)胞至感染發(fā)生部位,還可介導(dǎo)凋亡,細(xì)胞生長(zhǎng)以及血管生成。在其他病毒感染性疾病,如乙型肝炎病毒、丙型肝炎病毒、人免疫缺陷病毒、流感病毒、呼吸道輪狀病毒、鼻病毒、登革病毒等感染性疾病中,CXCL10均急劇升高,并與疾病的進(jìn)展及嚴(yán)重程度相關(guān)。CXCL10可趨化淋巴細(xì)胞至感染發(fā)生部位,發(fā)揮抗感染的功能;也可作為“細(xì)胞因子風(fēng)暴”中的一員加重機(jī)體炎癥反應(yīng),趨化淋巴細(xì)胞至病毒感染的靶細(xì)胞,引起靶細(xì)胞發(fā)生免疫病理?yè)p傷。所以,cxcl10究竟是起保護(hù)宿主的作用還是起損傷宿主的作用取決于宿主的免疫狀態(tài)及其基因背景。在htnv感染模型中,尚不清楚cxcl10可能發(fā)揮的作用。有研究發(fā)現(xiàn)很多信號(hào)通路如jak-stat途徑、pi3k/akt途徑以及traf2/tak1途徑可調(diào)控cxcl10的表達(dá),nf-κb、irf1和irf3等轉(zhuǎn)錄因子也被報(bào)道可結(jié)合于cxcl10的啟動(dòng)子區(qū)。盡管geimonen等報(bào)道htnv感染內(nèi)皮細(xì)胞可引起cxcl10的表達(dá)升高,但是對(duì)于htnv通過(guò)怎樣的途徑調(diào)控cxcl10產(chǎn)生仍不清楚。在本課題第一部分中,我們將解決兩個(gè)以下兩個(gè)問(wèn)題:(1)研究cxcl10在hfrs疾病中可能發(fā)揮的作用;(2)htnv通過(guò)怎樣的信號(hào)轉(zhuǎn)到途徑誘導(dǎo)cxcl10的產(chǎn)生。首先,我們收集了hfrs患者的血清,檢測(cè)hfrs患者血清中cxcl10的含量,并分析cxcl10的含量與病情之間的關(guān)系。隨后建立體外htnv感染原代內(nèi)皮細(xì)胞模型,探索cxcl的產(chǎn)生來(lái)源,并研究在內(nèi)皮細(xì)胞中,htnv調(diào)控cxcl10產(chǎn)生的可能的分子機(jī)制。在本研究中,我們發(fā)現(xiàn),hfrs患者血清中cxcl10表達(dá)急劇升高,在hfrs發(fā)病急性期尤為顯著。通過(guò)相關(guān)性分析我們發(fā)現(xiàn)cxcl10與hfrs患者的白細(xì)胞計(jì)數(shù)、尿素氮和血清肌酐呈正相關(guān),與血小板計(jì)數(shù)呈負(fù)相關(guān),且血漿病毒載量高的患者其cxcl10的水平也高。隨后通過(guò)檢測(cè)hfrs外周血淋巴細(xì)胞各亞群表面cxcl10受體cxcr3的表達(dá)水平,發(fā)現(xiàn)在hfrs發(fā)病急性期,單核細(xì)胞表面cxcr3急劇升高,提示在發(fā)病急性期,高水平的cxcl10可能可誘導(dǎo)單核細(xì)胞至內(nèi)皮細(xì)胞。在體外實(shí)驗(yàn)中我們發(fā)現(xiàn),htnv感染后的原代內(nèi)皮細(xì)胞可表達(dá)大量的cxcl10。而且,htnv并非通過(guò)其病毒蛋白調(diào)控cxcl10的表達(dá),而是通過(guò)其病毒rna中的dsrna結(jié)構(gòu),激活tlr3、rig-i和mda-5途徑,引起轉(zhuǎn)錄因子nf-κb和irf7發(fā)生磷酸化和核轉(zhuǎn)位,隨后nf-κb的亞基p50和p65以及irf7結(jié)合于cxcl10的啟動(dòng)子區(qū),調(diào)控cxcl10的轉(zhuǎn)錄過(guò)程。這些研究有助于我們理解cxcl10及其參與其中的“細(xì)胞因子風(fēng)暴”在病毒感染性疾病中的作用,可更好的為hfrs的治療提供理論依據(jù)。il-33是il-1細(xì)胞因子家族的新成員,以往研究發(fā)現(xiàn)il-33是“孤受體”st2的配體。在細(xì)胞處于靜止或凋亡狀態(tài)下,il-33可作為轉(zhuǎn)錄因子存在與細(xì)胞核內(nèi),當(dāng)細(xì)胞發(fā)生壞死,il-33則可從胞內(nèi)釋放。因此,il-33被認(rèn)為是“警報(bào)素”,作為危險(xiǎn)相關(guān)模式分子(danger-associatedmolecularpattern,damp)家族的成員,il-33的釋放可警示免疫系統(tǒng)機(jī)體受到感染或損傷。研究發(fā)現(xiàn),il-33可激活th2介導(dǎo)的免疫反應(yīng),促進(jìn)th2相關(guān)的細(xì)胞因子,如il-4、il-5和il-13的產(chǎn)生。在以th2免疫應(yīng)答介導(dǎo)的疾病中,il-33可引起內(nèi)皮細(xì)胞和上皮細(xì)胞發(fā)生炎癥反應(yīng)。il-33的受體st2由于編碼后對(duì)蛋白的剪切不同,可形成三種不同的蛋白剪切體,分別為膜表面st2l、膜表面變體型st2v和分泌至胞外的可溶型sst2�？扇苄蛃st2可作為il-33的誘餌受體,競(jìng)爭(zhēng)il-33與st2l的結(jié)合,中和il-33/st2l途徑激活后可產(chǎn)生的生理或病理效果。st2l與il-33結(jié)合后,st2l與il-1受體輔助蛋白(il-1raccessoryprotein,il-1racp)形成復(fù)合體,募集myd88,激活mapk和nf-κb途徑,促進(jìn)促炎因子的釋放。很多研究報(bào)道了il-33/st2途徑在不同疾病中的表達(dá)及作用。在呼吸道炎癥疾病、自身免疫性疾病和病毒感染性疾病中,il-33/st2途徑參與炎癥病理?yè)p傷的發(fā)生過(guò)程。然而在hfrs中,il-33/st2如何調(diào)控免疫反應(yīng)仍不清楚。在本課題的第二部分中,我們將解決以下兩個(gè)問(wèn)題:(1)研究il-33/st2途徑在hfrs中如何發(fā)揮免疫調(diào)節(jié)的作用;(2)研究il-33/st2與htnv感染協(xié)同作用誘導(dǎo)內(nèi)皮細(xì)胞炎癥反應(yīng)的分子機(jī)制。首先,我們收集hfrs患者血漿,檢測(cè)其血漿中il-33及sst2的含量,并分析二者與hfrs患者病情的相關(guān)性。隨后,在體外htnv感染內(nèi)皮細(xì)胞模型中,檢測(cè)il-33/st2對(duì)內(nèi)皮細(xì)胞發(fā)生炎癥反應(yīng)的調(diào)控。最后,應(yīng)用體外htnv感染內(nèi)皮細(xì)胞模型探索il-33/st2與htnv感染協(xié)同調(diào)控內(nèi)皮細(xì)胞炎癥反應(yīng)的分子機(jī)制。在本研究中,我們發(fā)現(xiàn)il-33及其誘餌受體sst2在hfrs血漿中均高表達(dá)。通過(guò)相關(guān)性分析發(fā)現(xiàn),il-33與sst2與患者病情嚴(yán)重程度均呈正相關(guān),且二者含量之間也呈正相關(guān)。隨后,我們?cè)隗w外htnv感染內(nèi)皮細(xì)胞模型中發(fā)現(xiàn),il-33可通過(guò)st2介導(dǎo)的途徑促進(jìn)htnv感染的內(nèi)皮細(xì)胞產(chǎn)生大量的促炎細(xì)胞因子,引起“細(xì)胞因子風(fēng)暴”,促進(jìn)內(nèi)皮細(xì)胞發(fā)生炎癥反應(yīng)。而sst2則可抑制內(nèi)皮細(xì)胞炎癥反應(yīng)的發(fā)生。而且,il-33和htnv可通過(guò)共同活化nf-κb途徑達(dá)到協(xié)同促進(jìn)炎癥反應(yīng)的作用。該研究提示IL-33可能是HTNV感染導(dǎo)致“細(xì)胞因子風(fēng)暴”的誘發(fā)因子,而該炎癥反應(yīng)的過(guò)程可被sST2抑制。IL-33/ST2共同調(diào)控HTNV感染后的免疫應(yīng)答,為治療HFRS提供了新的思路。
[Abstract]:Hantaan virus (Hantaan, virus, HTNV) infection in humans caused by severe 2%-10% of mortality rate of hemorrhagic fever with renal syndrome (hemorrhagic fever with renal syndrome, HFRS), there are approximately 100000 cases worldwide each year, more than 90% of which occurred in our country, Shaanxi Province as the main clinical manifestations of HFRS in patients with.HFRS fever, bleeding, platelet count decreased and acute renal insufficiency. Because the host rodent animal no disease manifestations of HTNV infection, due to the lack of a suitable animal model for HTNV infection, the pathogenic mechanism of HFRS is unclear. Dysfunction of platelet and endothelial cell injury is the main pathological manifestations of patients with HFRS. Research shows that excessive activation of the immune response and inflammation caused by "cytokine storm" may lead to the pathogenesis of HFRS. But the mechanism of HTNV infection by how The mechanisms leading to cytokine production and how to induce "cytokine storm" is not clear. In our previous work, the expression of a variety of cytokines in the serum of patients with HFRS were detected by using Luminex CXCL10 technology, which is an expression of cytokines with the highest.CXCL10 also known as IFN- gamma inducible protein 10, CXC is more members factor family, is mainly composed of endothelial cells, epithelial cells and keratinocytes secrete.CXCL10 and CXCR3 receptor binding, chemotaxis to lymphocyte infection, can mediate apoptosis, cell growth and angiogenesis. In other viral infections, such as hepatitis B virus, hepatitis C virus, human immunodeficiency respiratory virus, influenza virus, rotavirus, rhinovirus, dengue virus infection in CXCL10 were increased dramatically, and more with the progression of the disease and the severity of.CXCL10 Lymphocyte to infection, play anti infection function; also can be used as a member of "aggravated inflammation cytokine storm in the trend of lymphocyte to target cell virus infection, cause immune pathological injury occurred in target cells. Therefore, whether CXCL10 protects the host's role or function depends on the damage of the host the immune status of host and its genetic background. In the model of HTNV infection is not clear, CXCL10 may play a role. Some studies found that many signaling pathways such as JAK-STAT pathway, pi3k/akt pathway and traf2/tak1 pathway can regulate the expression of CXCL10, IRF1 and nf- kappa B, IRF3 transcription factors have been reported to be the promoter region binding to CXCL10. Although geimonen reported HTNV infection of endothelial cells can increase the expression of CXCL10, but for HTNV produced by the CXCL10 control approach is still not clear how. The first part of this paper, we will address the following two questions: two (1) of CXCL10 in HFRS may play a role in disease; (2) HTNV induced by CXCL10 through what way to signal generation. First, we collected the serum of HFRS patients, HFRS patients to detect the content of CXCL10 in serum, and analyze the relationship between the content and condition of CXCL10. Then the establishment of in vitro HTNV infection of primary endothelial cell model, explore the origin of CXCL, and studied in endothelial cells, the molecular mechanism of HTNV regulation of CXCL10. In this study, we found that the sharp increase in the expression of CXCL10 in sera of patients with HFRS, particularly significant during the acute phase of HFRS. Through correlation analysis, we found that white blood cell count CXCL10 and HFRS patients, serum creatinine and urea nitrogen were positively correlated, negatively correlated with platelet counts and plasma viral load in patients with high The level of CXCL10 is high. Then through the detection of peripheral blood HFRS lymphocyte subsets of CXCL10 receptor surface expression level of CXCR3, found in the acute phase of HFRS, monocyte surface CXCR3 increased sharply, suggesting that during the acute period, high level of CXCL10 may induce mononuclear cells to endothelial cells in vitro. We found that the primary endothelial cells after HTNV infection, the expression amount of cxcl10. and HTNV, not through the expression of viral proteins regulate CXCL10, but through the dsRNA structure, the RNA virus in the activation of TLR3, RIG-I and MDA-5 pathway, induced transcription factor nf- kappa B and IRF7 phosphorylation and nuclear translocation, start the sub area then nf- kappa B subunit P50 and p65 and IRF7 combined with CXCL10, the process of transcription regulation of CXCL10. These studies help us understand CXCL10 and participate in the "cytokine storm" in virus infection The clinical effect, can better provide a theoretical basis for the treatment of HFRS.Il-33 is a new member of IL-1 cytokine family, previous studies have shown that IL-33 is the ligand of ST2. The orphan receptor cells in a quiescent state or apoptosis, IL-33 can exist as a transcription factor and the nucleus, when cell necrosis, IL-33 can be released from cells. Therefore, IL-33 is considered to be the "alarm", as the danger associated molecular patterns (danger-associatedmolecularpattern, damp) family members, IL-33 can release warning immune system infection or injury. The study found that IL-33 can activate Th2 mediated immune response, promote Th2 related cytokines such as, IL-4, IL-5 and IL-13. In Th2 immune response mediated diseases, IL-33 endothelial cells and epithelial cells. The inflammatory reaction of.Il-33 receptor ST2 due to protein coding after shear All three proteins can form different shear different body, including membrane surface ST2L, soluble sst2., soluble sst2 membrane surface variant st2v and protein can be used as a decoy receptor for IL-33, IL-33 and ST2L combined with competition, physiological or pathological effects of.St2l and IL-33 can induce activation of il-33/st2l pathway and the combined ST2L and IL-1 receptor accessory protein (il-1raccessoryprotein, IL-1RAcP) to form a complex, raising MyD88, activation of MAPK and nf- kappa B pathway, promoting the release of inflammatory factors. Many studies reported the expression and role of il-33/st2 pathway in different diseases. In the airway inflammatory diseases, autoimmune diseases and virus infection the disease, the il-33/st2 pathway is involved in the damage process of pathological inflammation. However, in HFRS, il-33/st2 how to regulate the immune response remains unclear. In the second part of this paper, we will address the following Two questions: (1) il-33/st2 how to play the role of immunoregulation in HFRS; (2) the molecular mechanism of synergistic effect of endothelial cells induced by inflammatory reaction of il-33/st2 and HTNV infection. First, we collected plasma from patients with HFRS, IL-33 and sst2 were detected in plasma, and analyze the correlation between the disease and the two in patients with HFRS. Subsequently, in endothelial cells in vitro model of HTNV infection, regulation of detection of il-33/st2 inflammation on endothelial cells. Finally, application of HTNV infection in vitro endothelial cell model to explore the molecular mechanism of synergistic regulation of inflammation in endothelial cells il-33/st2 and HTNV infection. In this study, we found that IL-33 and sst2 were high decoy receptor the expression of HFRS in plasma. Through correlation analysis found that IL-33 and sst2 and the severity of the disease was positively correlated, and between the two were also positively correlated with. Later, we in the body HTNV infection was found in endothelial cell model, IL-33 pathway mediated by ST2 promote the production of proinflammatory cytokines of HTNV infected endothelial cells caused by "cytokine storm, promote endothelial cell inflammation. Sst2 can inhibit endothelial cell inflammation. Moreover, IL-33 and HTNV by CO activation of nf- kappa B pathway to synergistically promote inflammatory reaction. The study suggests that IL-33 may be induced by HTNV infection induced by cytokines and the process of the storm", the inflammatory reaction can be inhibited by sST2.IL-33/ST2 regulating immune response after HTNV infection control, provides a new way for the treatment of HFRS.

【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R512.8

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3 張衛(wèi)茹;侯凡凡;劉尚喜;郭志堅(jiān);周展眉;;晚期糖基化終產(chǎn)物增加動(dòng)脈粥樣硬化部位的炎癥反應(yīng)[A];“中華醫(yī)學(xué)會(huì)腎臟病學(xué)分會(huì)2004年年會(huì)”暨“第二屆全國(guó)中青年腎臟病學(xué)術(shù)會(huì)議”論文匯編[C];2004年

4 濮紅梅;尹忠誠(chéng);劉秉成;李勝開(kāi);馮錦紅;;血液透析患者血清IL-10與炎癥反應(yīng)及營(yíng)養(yǎng)狀況的關(guān)系研究[A];中華醫(yī)學(xué)會(huì)腎臟病學(xué)分會(huì)2006年學(xué)術(shù)年會(huì)論文集[C];2006年

5 陸志偉;黃慧;姜純國(guó);徐作軍;;輔助性T淋巴細(xì)胞與特發(fā)性肺間質(zhì)纖維化關(guān)系的初步研究[A];中華醫(yī)學(xué)會(huì)呼吸病學(xué)年會(huì)——2011（第十二次全國(guó)呼吸病學(xué)學(xué)術(shù)會(huì)議）論文匯編[C];2011年

6 俞佳;王仲;;內(nèi)源性氣體信號(hào)分子硫化氫與炎癥反應(yīng)[A];中華醫(yī)學(xué)會(huì)急診醫(yī)學(xué)分會(huì)第十三次全國(guó)急診醫(yī)學(xué)學(xué)術(shù)年會(huì)大會(huì)論文集[C];2010年

7 周曉艷;徐營(yíng)營(yíng);謝兆宏;許繼平;畢建忠;;炎癥反應(yīng)與神經(jīng)系統(tǒng)變性疾病的研究進(jìn)展[A];2011全國(guó)老年癡呆與衰老相關(guān)疾病學(xué)術(shù)會(huì)議第三屆山東省神經(jīng)內(nèi)科醫(yī)師（學(xué)術(shù)）論壇論文匯編[C];2011年

8 張會(huì)云;崔克亮;曹書(shū)華;;炎癥反應(yīng),凝血機(jī)制與MODS的發(fā)病機(jī)理的關(guān)系[A];中華醫(yī)學(xué)會(huì)急診分會(huì)第五屆全國(guó)危重病學(xué)術(shù)交流會(huì)論文匯編[C];2004年

9 燕艷麗;邱海波;楊毅;許紅陽(yáng);王麗;孫輝明;;急性呼吸窘迫綜合征家兔肺部及肺外器官炎癥反應(yīng)的變化[A];第六屆全國(guó)危重病學(xué)術(shù)交流大會(huì)論文匯編[C];2005年

10 周曉艷;徐營(yíng)營(yíng);謝兆宏;許繼平;畢建忠;;炎癥反應(yīng)與神經(jīng)系統(tǒng)變性疾病的研究進(jìn)展[A];山東省第三次中西醫(yī)結(jié)合神經(jīng)內(nèi)科學(xué)術(shù)研討會(huì)論文匯編[C];2011年

中國(guó)重要報(bào)紙全文數(shù)據(jù)庫(kù) 前10條

1 楊一唯邋記者 王春;我科學(xué)家發(fā)現(xiàn)調(diào)節(jié)人體炎癥反應(yīng)新機(jī)制[N];科技日?qǐng)?bào);2007年

2 王蔚;我國(guó)科學(xué)家發(fā)現(xiàn)調(diào)節(jié)人體炎癥反應(yīng)新機(jī)制[N];大眾科技報(bào);2007年

3 記者 徐瑞哲;第三者“插足”抑制炎癥反應(yīng)[N];解放日?qǐng)?bào);2007年

4 記者白毅;炎癥反應(yīng)中淋巴結(jié)重塑新機(jī)制被揭示[N];中國(guó)醫(yī)藥報(bào);2011年

5 記者 耿挺;尋找炎癥反應(yīng)蛋白[N];上�？萍紙�(bào);2007年

6 信文;“IL-10”蛋白調(diào)節(jié)炎癥反應(yīng)[N];醫(yī)藥經(jīng)濟(jì)報(bào);2002年

7 知陶;把炎癥反應(yīng)排除在外[N];醫(yī)藥經(jīng)濟(jì)報(bào);2002年

8 韓秀霞;Capase-12蛋白參與炎癥反應(yīng)[N];中國(guó)醫(yī)藥報(bào);2005年

9 范曉艷;免疫系統(tǒng)“出錯(cuò)” 救星變?yōu)男荹N];醫(yī)藥經(jīng)濟(jì)報(bào);2003年

10 高春東;軟組織挫傷用抗生素?zé)o效[N];大眾衛(wèi)生報(bào);2004年

中國(guó)博士學(xué)位論文全文數(shù)據(jù)庫(kù) 前10條

1 段二珍;HMGB1在PRRSV感染中的作用及Glycyrrhizin抗PRRSV活性研究[D];華中農(nóng)業(yè)大學(xué);2014年

2 韋超;GIT2抑制TLR介導(dǎo)的炎癥反應(yīng)[D];北京協(xié)和醫(yī)學(xué)院;2013年

3 楊瀟;草魚(yú)白細(xì)胞介素1β誘導(dǎo)表達(dá)的負(fù)調(diào)控機(jī)制及其在炎癥反應(yīng)中的意義[D];電子科技大學(xué);2014年

4 王超;豬繁殖與呼吸綜合征病毒（PRRSV）調(diào)控NLRP3介導(dǎo)的炎癥反應(yīng)的分子機(jī)制研究[D];西北農(nóng)林科技大學(xué);2015年

5 趙力;MiR-214與腺苷A2A受體相互調(diào)控的分子機(jī)制及其在炎癥反應(yīng)中的作用研究[D];第三軍醫(yī)大學(xué);2015年

6 NURULIARIZKI SHINTA;[D];華中農(nóng)業(yè)大學(xué);2016年

7 張宇絲;漢灘病毒感染引起血管內(nèi)皮細(xì)胞炎癥因子的產(chǎn)生及誘發(fā)炎癥反應(yīng)的機(jī)制[D];第四軍醫(yī)大學(xué);2016年

8 吳越;載脂蛋白E及其擬肽COG1410對(duì)蛛網(wǎng)膜下腔出血后早期腦損傷和炎癥反應(yīng)的影響[D];重慶醫(yī)科大學(xué);2016年

9 李吉林;Toll-like receptor2/4在冠狀動(dòng)脈內(nèi)皮細(xì)胞炎癥反應(yīng)調(diào)控中的作用[D];南方醫(yī)科大學(xué);2011年

10 柳楠;腸道病毒分子流行病學(xué)及腸道病毒71型感染致炎癥反應(yīng)機(jī)制研究[D];中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院;2014年

中國(guó)碩士學(xué)位論文全文數(shù)據(jù)庫(kù) 前10條

1 要萌萌;Mdx小鼠骨骼肌中炎癥反應(yīng)和mpeg1的表達(dá)[D];河北醫(yī)科大學(xué);2015年

2 張曉瑩;去鐵胺對(duì)脂多糖誘發(fā)的小鼠中樞神經(jīng)炎癥反應(yīng)與記憶損傷的改善作用[D];中國(guó)人民解放軍醫(yī)學(xué)院;2015年

3 陳凱;纈沙坦對(duì)糖尿病大鼠腎臟內(nèi)質(zhì)網(wǎng)應(yīng)激及炎癥反應(yīng)的抑制作用[D];安徽醫(yī)科大學(xué);2015年

4 張凱;MiR-322負(fù)調(diào)控LPS誘導(dǎo)炎癥反應(yīng)的機(jī)制研究[D];華中農(nóng)業(yè)大學(xué);2015年

5 李雪寒;HSPA12B在抑制LPS所致內(nèi)皮細(xì)胞炎癥反應(yīng)中的必要性研究[D];南京醫(yī)科大學(xué);2015年

6 曹春琪;麥冬不同部位對(duì)巨噬細(xì)胞炎癥反應(yīng)的調(diào)節(jié)作用及其物質(zhì)基礎(chǔ)研究[D];北京中醫(yī)藥大學(xué);2016年

7 穆衛(wèi)濤;LPS誘導(dǎo)雞幾個(gè)炎癥反應(yīng)相關(guān)基因的表達(dá)調(diào)控研究[D];哈爾濱師范大學(xué);2016年

8 趙蘭婷;NOTCH信號(hào)通路對(duì)慢性阻塞性肺疾病炎癥反應(yīng)的影響及機(jī)制研究[D];蘭州大學(xué);2015年

9 徐士欣;活化血小板在急性缺血性腦卒中后炎癥反應(yīng)中作用機(jī)制的研究[D];天津醫(yī)科大學(xué);2007年

10 劉宏;線粒體DNA編碼蛋白質(zhì)在炎癥反應(yīng)中作用的初步探討[D];中國(guó)人民解放軍醫(yī)學(xué)院;2013年

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