本文選題：缺氧復(fù)氧 + SOCS-3�。� 參考：《南昌大學(xué)》2017年博士論文

【摘要】：背景:缺血性心臟病(ischemic heart disease,IHD)是一種常見的危害人類健康的疾病,僅2012年一年死亡人數(shù)就達(dá)740萬。并且,IHD耗費醫(yī)療資源驚人,通過溶栓、PCI等治療手段盡快恢復(fù)冠狀動脈血流供應(yīng)是挽救患者生命的關(guān)鍵,但研究發(fā)現(xiàn)心肌缺血持續(xù)一段時間后,重新恢復(fù)血流灌注會給心臟組織帶來新的損傷,出現(xiàn)心肌頓抑、心功能降低及惡性心律失常發(fā)作等繼發(fā)性心肌損害——缺血再灌注損傷(ischemia-reperfusion injury,IRI)。研究心臟缺血再灌注損傷的發(fā)生機制,探討有效的IRI心肌保護措施長期以來都是心血管病醫(yī)生孜孜以求的夢想。目前認(rèn)為,心臟缺血再灌注損傷與心肌線粒體能量代謝障礙、細(xì)胞內(nèi)鈣超載、氧自由基釋放和細(xì)胞凋亡等有關(guān)。細(xì)胞因子信號轉(zhuǎn)導(dǎo)抑制因子(suppressor of cytokine signaling,SOCS)家族是特征性SOCS盒胞漿蛋白分子家族,包括SH2核心結(jié)構(gòu)及具有保守性的C端40個氨基酸模塊。該家族存在多種細(xì)胞內(nèi)并可被誘導(dǎo)表達(dá)。目前發(fā)現(xiàn)該家族有CIS(the cytokine-inducible SH2 domain-containing protein)、SOCS1-7等8個成員分子。SOCS通過競爭結(jié)合JAK催化位點從而抑制JAK信號通路。其中SOCS1與SOCS3同源性最強,與心血管疾病關(guān)系最為密切。既往研究發(fā)現(xiàn)SOCS1競爭心肌營養(yǎng)素-1(cardiotrophin-1,CT-1)下游信號通路JAK的催化位點,從而抑制JAK-STAT3信號轉(zhuǎn)導(dǎo)通路,導(dǎo)致心肌細(xì)胞凋亡增加及心肌梗死面積擴大。Micro RNA(miRNA)是一類內(nèi)生的、長度約為18~25個核苷酸的小RNA,通過對靶m RNA降解或者翻譯抑制在轉(zhuǎn)錄后水平發(fā)揮對靶基因負(fù)調(diào)控作用。參與細(xì)胞內(nèi)多種重要調(diào)節(jié)。研究發(fā)現(xiàn)miRNA參與了心臟發(fā)育、心肌肥厚及重塑、心律失常、心力衰竭及心肌細(xì)胞凋亡等病理生理過程。在心肌成纖維細(xì)胞中,miR-19a通過調(diào)控TGF-βR II抑制自噬。又有報道m(xù)iR-19與心肌細(xì)胞凋亡有關(guān);最近研究發(fā)現(xiàn)miR-19b在心臟缺血再灌注損傷中通過調(diào)控PTEN抑制心肌細(xì)胞凋亡。鑒于miR-19a與miR-19b同源于miR-17-92基因簇,miR-19a極有可能參與心臟缺血再灌注損傷。最近又有研究發(fā)現(xiàn),在肝細(xì)胞中miR-19a靶向抑制SOCS3表達(dá)增加JAK-STAT的轉(zhuǎn)錄并促進肝細(xì)胞增殖。由此我們推測,在缺血再灌注損傷過程中,miR-19a可能通過靶向調(diào)控SOCS3抑制心肌細(xì)胞凋亡。綜上所述,我們推測在心肌IRI過程中可能存在的一個調(diào)控過程:心肌IRI時保護性細(xì)胞因子(比如CT-1等)表達(dá)上調(diào),誘導(dǎo)JAK-STAT3活性增強,導(dǎo)致STAT3磷酸化活性增強可以上調(diào)SOCS3表達(dá),SOCS3反過來競爭結(jié)合JAK并抑制其表達(dá),抵消一部分STAT3對心肌細(xì)胞抗凋亡作用。如果miR-19a能抑制SOCS3的表達(dá),間接提高JAK-STAT3的活性并增強在IRI中的抗凋亡作用。為了證實這一推測。本研究進行一下三方面的探索:首先,通過離體實驗探討SOCS3在缺血再灌注損傷中的促凋亡作用,將建立心肌細(xì)胞缺氧復(fù)氧模型,通過細(xì)胞存活率檢查、生化檢測等體外實驗證實SOCS3與促凋亡蛋白Bim之間的關(guān)系。其次,在離體實驗探討miR-19a對SOCS3靶向調(diào)控作用機制。通過miR-19a過表達(dá)及抑制實驗檢測SOCS3的蛋白表達(dá)以及對心肌細(xì)胞凋亡的影響。第三,為探討SOCS-3與急性心肌梗死具有相關(guān)性,以急性心肌梗死患者作為研究對象,分析高表達(dá)SOCS3是否可以預(yù)測心臟主要不良事件。第一部分探討在心肌細(xì)胞缺氧復(fù)氧過程中SOCS3與Bim之間的關(guān)系及對細(xì)胞凋亡的影響目的:建立H9c2心肌細(xì)胞缺氧復(fù)氧模型,明確SOCS3在心肌細(xì)胞缺氧復(fù)氧中對Bim表達(dá)影響及細(xì)胞凋亡的影響。方法:1)培養(yǎng)H9c2心肌細(xì)胞。2)模擬缺血再灌注損傷建立缺氧復(fù)氧(Hypoxia reoxygenation,HR)模型,Western-blot檢測SOCS3表達(dá)。3)設(shè)計與合成3對靶向SOCS3基因的si RNA(SOCS3-si RNA),Western-blot篩選最佳SOCS3-si RNA。4)將效果最佳SOCS3-si RNA轉(zhuǎn)染H9c2,給予缺氧復(fù)氧。實驗分4組:空白對照組(Control組)、HR組、HR+Negative Control組、HR+SOCS3-si RNA組;5)用CCK8法檢測細(xì)胞增殖活力,Flow cytometry檢測細(xì)胞凋亡率,Western-blot技術(shù)分別測定SOCS3、凋亡相關(guān)基因Bim、Bax和Bcl-2凋亡蛋白的表達(dá)。結(jié)果:1)缺氧復(fù)氧模過程中SOCS3表達(dá)明顯上調(diào)。2)與空白對照組相比,HR組細(xì)胞存活率明顯減少(P0.05),SOCS3-si RNA組H9c2存活率明顯增加(P0.05),凋亡率明顯下降(P0.05);3)與HR組相比,SOCS3-si RNA+HR組Bim表達(dá)下調(diào)(P0.01);4)與HR組相比,SOCS3-si RNA+HR組,Bcl-2表達(dá)上調(diào),Bax表達(dá)下調(diào),Bcl-2/Bax比值增大(P0.05)。結(jié)論:1)H9c2心肌細(xì)胞在缺氧復(fù)氧后,SOCS3表達(dá)明顯升高;2)在心肌細(xì)胞缺氧復(fù)氧模型中,沉默SOCS3可以下調(diào)Bim和Bax的表達(dá);3)在心肌細(xì)胞在缺氧復(fù)氧模型中,沉默SOCS3可以上調(diào)Bcl-2的表達(dá)4)在心肌細(xì)胞在缺氧復(fù)氧模型中,沉默SOCS3可以升高細(xì)胞活力,減少細(xì)胞凋亡。第二部分:缺氧復(fù)氧心肌細(xì)胞中SOCS3對JAK-STAT3信號通路的影響及miR-19a對其調(diào)控作用目的:本研究擬建立H9c2心肌細(xì)胞HR模型,測定miR-19a在HR過程中表達(dá),在H9c2中轉(zhuǎn)染miR-19a mimics或miR-19a inhibitor調(diào)控miR-19a的表達(dá),測定細(xì)胞SOCS3的表達(dá)及細(xì)胞凋亡率、凋亡相關(guān)基因蛋白表達(dá)水平,探討miR-19a在心肌細(xì)胞缺氧復(fù)氧中對SOCS3調(diào)控作用及介導(dǎo)HR細(xì)胞凋亡的影響。方法:1)模擬缺血再灌注損傷建立HR模型,q RT-PCR檢測miR-19a表達(dá)。2)使用Lipofectamine3000分別將miR-19a mimics及miR-19a inhibitor轉(zhuǎn)染入H9c2細(xì)胞,給予缺氧復(fù)氧。3)實驗分6組:空白對照組(Control組)、HR、HR+mimics Negative Control、HR+miR-19a mimics組、HR+Mirco RNA inhibitor Negative Control組、HR+miR-19a inhibitor組;4)CCK8檢測細(xì)胞活力,Flow cytometry檢測細(xì)胞凋亡率,Western-blot技術(shù)分別測定SOCS3、p-STAT3、STAT3、Caspases、Bim、Bax和Bcl-2的表達(dá)。結(jié)果:1)HR過程中miR-19a表達(dá)明顯下調(diào)。2)HR組較control組細(xì)胞存活率明顯減少(P0.05),miR-19a mimics組H9c2細(xì)胞存活率明顯增加(P0.05),凋亡率明顯下降(P0.05);miR-19a inhibitor組H9c2細(xì)胞存活率明顯下降(P0.05),凋亡率明顯增加(P0.05);3)過表達(dá)miR-19a明顯抑制SOCS3、Caspases、Bim及Bax蛋白表達(dá),上調(diào)p-STAT3活性及Bcl-2蛋白,抑制細(xì)胞凋亡。4)抑制miR-19a明顯上調(diào)SOCS3、Caspases、Bim及Bax蛋白表達(dá),抑制 p-STAT3活性,Bcl-2表達(dá)下調(diào),促進凋亡。結(jié)論:1)H9c2心肌細(xì)胞缺氧復(fù)氧后,miR-19a表達(dá)明顯下調(diào);2)心肌細(xì)胞缺氧復(fù)氧過程中,miR-19a可能通過調(diào)控SOCS3發(fā)揮抗凋亡作用;第三部分血漿SOCS-3上調(diào)與急性心肌梗死不良預(yù)后相關(guān)性分析目的:人血漿SOCS-3上調(diào)與急性心肌梗死不良預(yù)后相關(guān)性分析方法:入選2016.3-2016.10在我院就診急性心肌梗死(AMI)患者(n=68),同期選擇年齡、性別等相匹配的,無心血管系統(tǒng)疾病的自愿者作為健康對照組(n=20)。采用酶聯(lián)免疫(ELISA)測定SOCS3、c Tn I和CK-MB。并將SOCS3與c Tn I、CK-MB、NT-pro BNP、e GFR、左室射血分?jǐn)?shù)(left ventricular ejection fraction LVEF)、冠狀動脈病變血管數(shù)、Killip心功能分級和主要不良心血管事件(MACE)等行相關(guān)分析。結(jié)果:AMI患者血漿SOCS-3表達(dá)水平顯著高于健康對照組(P0.01);通過ROC曲線比較,血漿SOCS-3區(qū)分AMI患者的敏感性和特異性分別為70.0和85.5(AUC=0.856)。SOCS-3水平與高血壓(P=0.002),左心室射血分?jǐn)?shù)(LVEF)(P=0.004),e GFR(P0.001),c Tn I(P0.001),CK-MB(P0.001),NT-pro BNP(P0.001)等臨床病理參數(shù)顯著相關(guān)。此外,AMI患者冠狀動脈狹窄數(shù)目越多,血漿SOCS-3水平越高。SOCS-3水平與Killip心功能分級相關(guān),Killip心功能分級越高的患者血漿SOCS-3水平越高。AMI患者中,根據(jù)兩分位中位數(shù),高血漿SOCS-3比低血漿SOCS-3患者具有更高主要不良心血管事件(MACE)發(fā)生率(P0.01)。同樣,高血漿SOCS-3較低血漿SOCS-3患者,6個月總體存活率更低(P0.01)。血漿SOCS3是MACE的獨立危險因素。結(jié)論:SOCS-3是預(yù)測急性心肌梗死預(yù)后有價值的生物學(xué)標(biāo)指標(biāo)�？傊�,從分子、細(xì)胞和在體多層面證實通過抑制SOCS3的表達(dá)減輕缺血再灌注心肌損傷,為深入理解SOCS3的調(diào)控機制進而對心肌保護機制做有益的探索。
[Abstract]:Background: ischemic heart disease (IHD) is a common disease that endangers human health. The number of deaths in one year is 7 million 400 thousand in 2012 alone. And, IHD has a surprising number of medical resources. By thrombolytic and PCI treatment, the key to restore the blood flow of the coronary artery as soon as possible is the key to save the life of the patients, but the study found myocardial deficiency. After a period of blood continuous time, a new recovery of blood perfusion will bring new damage to the heart tissue, and secondary myocardial damage, such as myocardial stunning, cardiac dysfunction and malignant arrhythmia attack, such as ischemia-reperfusion injury (IRI). The mechanism of myocardial ischemia reperfusion injury is studied, and the effective IRI is explored. Myocardial protection has long been the dream of cardiovascular doctors. It is believed that myocardial ischemia reperfusion injury is related to myocardial mitochondrial energy metabolism disorder, intracellular calcium overload, oxygen free radical release and cell apoptosis. Cytokine signal transduction inhibitor (suppressor of cytokine signaling, SOCS) family is The characteristic SOCS box cytoplasmic protein family, including the SH2 core structure and the conserved C terminal 40 amino acid modules. The family exists in a variety of cells and can be induced to be induced. At present, the family has CIS (the cytokine-inducible SH2 domain-containing protein), and SOCS1-7 and other 8 members are.SOCS through competition and JAK. Inhibition of JAK signaling pathways. Among them, SOCS1 and SOCS3 have the strongest homology and are most closely related to cardiovascular disease. Previous studies have found that SOCS1 competitive cardiomyotrophic -1 (cardiotrophin-1, CT-1) downstream signal pathway JAK's catalytic site, thus inhibiting the JAK-STAT3 signal transduction pathway, leading to increased cardiomyocyte apoptosis and myocardial infarction Area enlargement of.Micro RNA (miRNA) is a class of endogenous, small RNA with a length of about 18~25 nucleotides. By degrading the target m RNA or suppressing the negative regulation of the target gene at post transcriptional levels, it participates in a variety of important intracellular regulations. The study found miRNA involved in heart development, cardiac hypertrophy and remodeling, arrhythmia, and heart failure. The pathophysiological processes such as exhaustion and cardiomyocyte apoptosis. In myocardial fibroblasts, miR-19a inhibits autophagy by regulating TGF- beta R II. It is also reported that miR-19 is associated with cardiomyocyte apoptosis; recent studies have found that miR-19b inhibits cardiomyocyte apoptosis by regulating PTEN in ischemic reperfusion injury. In view of miR-19a and miR-19b homologous to miR-17 -92 gene cluster, miR-19a may be very likely to participate in the ischemic reperfusion injury of the heart. Recently, it has been found that the expression of miR-19a targeting inhibition of SOCS3 in hepatocytes increases the transcription of JAK-STAT and promotes the proliferation of hepatocytes. Thus, we speculate that in the course of ischemia reperfusion injury, miR-19a can inhibit the apoptosis of cardiac myocytes through the targeting regulation of SOCS3. In summary, we speculate that a regulatory process may exist during the IRI process in the myocardium: the expression of protective cytokines (such as CT-1, such as CT-1, etc.) is up up and induces the enhancement of JAK-STAT3 activity, which leads to the increase of the STAT3 phosphorylation activity to up regulate the expression of SOCS3. SOCS3, in turn, competes with JAK and inhibits its expression, counteracts a part of STAT3 against the heart. The anti apoptosis effect of muscle cells. If miR-19a can inhibit the expression of SOCS3, indirectly improve the activity of JAK-STAT3 and enhance the anti apoptosis effect in IRI. In order to confirm this speculations, this study carries out three aspects of this study: first, to explore the effect of SOCS3 on the apoptosis of ischemia reperfusion injury and to establish cardiomyocytes in vitro. Hypoxic reoxygenation model, the relationship between SOCS3 and apoptotic protein Bim was confirmed by cell survival test, biochemical test in vitro. Secondly, in vitro, the mechanism of miR-19a on the targeting of SOCS3 was investigated. The expression of protein and the effect of SOCS3 on the apoptosis of myocardial cells were detected by miR-19a overexpression and inhibition experiment. Third, third, In order to investigate the correlation between SOCS-3 and acute myocardial infarction, the patients with acute myocardial infarction were used as the research object to analyze whether the high expression of SOCS3 could predict the major adverse events of the heart. The first part was to explore the relationship between SOCS3 and Bim in the process of myocardial anoxia reoxygenation and the effect on the apoptosis of the cells: the establishment of H9c2 cardiac myocytes. Hypoxia reoxygenation model was used to determine the effect of SOCS3 on Bim expression and apoptosis in hypoxia reoxygenation. Methods: 1) cultured H9c2 myocardial cells.2) simulated ischemia reperfusion injury (Hypoxia reoxygenation, HR) model, Western-blot detection SOCS3 expression.3), designed and synthesized 3 targets for SOCS3 gene Si RNA), Western-blot screened the best SOCS3-si RNA.4) to transfect the best SOCS3-si RNA into H9c2 and give hypoxia reoxygenation. The experiment was divided into 4 groups: blank control group (Control group), HR group, HR+Negative Control group, and 5) detection of cell proliferation activity. CS3, the expression of apoptosis related genes Bim, Bax and Bcl-2 apoptosis protein. Results: 1) SOCS3 expression was obviously up regulated in the process of hypoxia reoxygenation. Compared with the blank control group, the survival rate of the HR group decreased significantly (P0.05), the H9c2 survival rate in the SOCS3-si RNA group was significantly increased (P0.05) and the apoptosis rate decreased significantly (3). Down regulation of expression (P0.01); 4) compared with group HR, SOCS3-si RNA+HR group, Bcl-2 expression was up regulation, Bax expression was down, Bcl-2/Bax ratio increased (P0.05). Conclusion: 1) H9c2 myocardial cells in hypoxia reoxygenation, SOCS3 expression increased obviously; 2) in the hypoxic reoxygenation model of cardiac myocytes, silence SOCS3 can reduce the expression of Bim and expressions; 3) in the myocardial cells in anoxia complex In oxygen model, silent SOCS3 can increase the expression of Bcl-2 4) in the hypoxic reoxygenation model, silent SOCS3 can increase cell viability and reduce cell apoptosis. Second part: the effect of SOCS3 on JAK-STAT3 signaling pathway in anoxic reoxygenated cardiomyocytes and the purpose of miR-19a to regulate it: This study is to establish a HR model for H9c2 cardiomyocytes. The expression of miR-19a in the process of HR, miR-19a mimics or miR-19a inhibitor were transfected in H9c2 to regulate the expression of miR-19a, and the expression of SOCS3, the rate of apoptosis, the expression level of apoptosis related gene protein, and the effect of miR-19a on SOCS3 in the hypoxia reoxygenation of cardiomyocytes and the effect of inducing apoptosis of HR cells were investigated. Method: 1) HR model was established for simulated ischemia reperfusion injury, and miR-19a expression.2 was detected by Q RT-PCR). MiR-19a mimics and miR-19a inhibitor were transfected into H9c2 cells using Lipofectamine3000 respectively. The experiment was divided into 6 groups: blank control group. Tive Control group, HR+miR-19a inhibitor group; 4) CCK8 detection of cell viability, Flow cytometry detection of cell apoptosis rate, Western-blot technology to determine SOCS3, p-STAT3, STAT3, Caspases, Caspases, expressions and expressions. The survival rate of H9c2 cells in group s was significantly increased (P0.05), the rate of apoptosis decreased significantly (P0.05), the survival rate of H9c2 cells in miR-19a inhibitor group decreased significantly (P0.05), the apoptosis rate was significantly increased (P0.05); 3) the overexpression miR-19a obviously inhibited SOCS3, Caspases, protein, inhibition of apoptosis and inhibition of apoptosis The expression of SOCS3, Caspases, Bim and Bax protein was up-regulated, the activity of p-STAT3 was inhibited and the expression of Bcl-2 was down regulated. Conclusion: 1) the expression of miR-19a in H9c2 cardiomyocytes was obviously down regulated after hypoxia reoxygenation; 2) in the process of hypoxia reoxygenation of cardiac myocytes, miR-19a may be mediated by the regulation of apoptosis in SOCS3; the third part of plasma SOCS-3 up regulation and acute myocardium Correlation analysis of poor prognosis Objective: an analysis of the correlation between the up-regulation of human plasma SOCS-3 and the poor prognosis of acute myocardial infarction: 2016.3-2016.10 was selected in the patients with acute myocardial infarction (AMI) in our hospital (n=68), the selection of age and sex in the same period, and the volunteers with no heart blood tube system disease as the healthy control group (n=20). Enzyme linked immunosorbent assay (ELISA) for the determination of SOCS3, C Tn I and CK-MB. and the correlation analysis of SOCS3 and C Tn I, CK-MB, NT-pro, left ventricular ejection fraction, coronary artery disease, cardiac function classification and major adverse cardiovascular events. Compared with the healthy control group (P0.01), the sensitivity and specificity of plasma SOCS-3 in AMI patients were 70 and 85.5 (AUC=0.856).SOCS-3, respectively, with hypertension (P=0.002), left ventricular ejection fraction (P=0.004), e GFR (P0.001), e GFR, and other clinicopathological parameters. In addition, the more coronary stenosis in AMI patients, the higher the plasma SOCS-3 level, the.SOCS-3 level was associated with the Killip cardiac function classification. The higher the level of Killip cardiac function, the higher the plasma SOCS-3 level in patients with.AMI, the higher plasma SOCS-3 than the low plasma SOCS-3 patients had higher major adverse cardiovascular events (MA), according to the median of the binary position (MA). CE) incidence (P0.01). Similarly, high plasma SOCS-3 in patients with lower plasma SOCS-3 has a lower overall survival rate for 6 months (P0.01). Plasma SOCS3 is an independent risk factor for MACE. Conclusion: SOCS-3 is a valuable biological marker for predicting the prognosis of acute myocardial infarction. Myocardial ischemia and reperfusion injury can help us to understand the regulatory mechanism of SOCS3 and further explore the mechanism of myocardial protection.

【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R541

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2 邢長英;歸綏琪;;SOCS3作用機制與婦產(chǎn)科研究進展[J];生殖與避孕;2007年04期

3 ;Expression of SOCS-1 in the liver tissues of chronic hepatitis B and its clinical significance[J];World Journal of Gastroenterology;2008年04期

4 ;Dendritic Cells Transduced with SOCS1 Gene Exhibit Regulatory DC Properties and Prolong Allograft Survival[J];Cellular & Molecular Immunology;2009年02期

5 許文頻;李衛(wèi)東;;SOCS3分子——治療人類多種疾病的潛在靶標(biāo)[J];藥學(xué)學(xué)報;2011年07期

6 李詠;韓梅芳;李維娜;師愛超;張元亞;王宏艷;王發(fā)席;李蘭;吳婷;丁琳;陳韜;嚴(yán)偉明;羅小平;寧琴;;SOCS3 Expression Correlates with Severity of Inflammation in Mouse Hepatitis Virus Strain 3-induced Acute Liver Failure and HBV-ACLF[J];Journal of Huazhong University of Science and Technology(Medical Sciences);2014年03期

7 毛一雷,Ling P Bistrian BR,Smith RJ Joslin;新發(fā)現(xiàn)的SOCS蛋白家族:揭示了創(chuàng)傷和營養(yǎng)不良時代謝異常的機理[J];中國臨床營養(yǎng)雜志;2000年01期

8 ;Gene Delivery of SOCS3 Protects Mice from Lethal Endotoxic Shock[J];Cellular & Molecular Immunology;2005年05期

9 周運恒;榮光華;楊再興;仲人前;;SOCS及其免疫學(xué)作用研究進展[J];現(xiàn)代免疫學(xué);2007年06期

10 張奇;吳健;于波;;SOCS1與免疫調(diào)節(jié)的研究進展[J];免疫學(xué)雜志;2010年11期

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1 Zhiyao Bao;Quirui Zhang;Huanying Wan;Min Zhou;Ping He;;Expression of SOCS-1 in the peripheral blood from patients with idiopathic pulmonary fibrosis[A];中華醫(yī)學(xué)會呼吸病學(xué)年會——2013第十四次全國呼吸病學(xué)學(xué)術(shù)會議論文匯編[C];2013年

2 徐雪;李娟;王亞軍;;家雞細(xì)胞因子信號傳導(dǎo)抑制因子(SOCS1)基因的克隆及其組織表達(dá)[A];四川省動物學(xué)會第九次會員代表大會暨第十屆學(xué)術(shù)研討會論文集[C];2011年

3 王國兵;李成榮;楊軍;溫鵬強;賈實磊;;SOCS1/SOCS3甲基化改變在兒童急性ITP Th17/Treg細(xì)胞失衡中的作用初探[A];中華醫(yī)學(xué)會第十七次全國兒科學(xué)術(shù)大會論文匯編（上冊）[C];2012年

4 許衍碩;陳志斌;梁艷冰;唐皓;馬中富;;外周血單個核細(xì)胞SOCS-1表達(dá)與MODS患者預(yù)后關(guān)系的研究[A];全國危重病急救醫(yī)學(xué)學(xué)術(shù)會議論文匯編[C];2007年

5 許衍碩;陳志斌;梁艷冰;唐皓;馬中富;;外周血單個核細(xì)胞SOCS-1表達(dá)與MODS患者預(yù)后關(guān)系的研究[A];2008年廣東省中醫(yī)熱病、急癥、中西醫(yī)結(jié)合急救、危重病、災(zāi)害醫(yī)學(xué)學(xué)術(shù)會議學(xué)術(shù)論文集[C];2008年

6 譚峰;方美鳳;梁艷桂;劉曉林;陳文霖;;急性腦梗塞患者血清SOCS-3的動態(tài)變化及其意義[A];國家中醫(yī)藥管理局腦病重點研究室建設(shè)研討會暨中風(fēng)病科研成果推廣交流會論文匯編[C];2010年

7 夏杰;步宏;石毓君;孫懷強;包驥;;部分肝切除后肝再生過程中SOCS3基因啟動子甲基化檢測[A];中華醫(yī)學(xué)會病理學(xué)分會2010年學(xué)術(shù)年會日程及論文匯編[C];2010年

8 陳志斌;梁艷冰;唐皓;林賢壽;何東華;馬中富;;外周血單個核細(xì)胞SOCS-1與SOCS-3表達(dá)與MODS患者預(yù)后關(guān)系的研究[A];2008年廣東省中醫(yī)熱病、急癥、中西醫(yī)結(jié)合急救、危重病、災(zāi)害醫(yī)學(xué)學(xué)術(shù)會議學(xué)術(shù)論文集[C];2008年

9 劉霞;張永亮;安華章;徐紅梅;于益芝;楊曉;曹雪濤;;SOCS3反饋抑制巨噬細(xì)胞內(nèi)源性TGF-β1負(fù)向調(diào)節(jié)TLR4反應(yīng)的作用和機制研究[A];中國免疫學(xué)會第五屆全國代表大會暨學(xué)術(shù)會議論文摘要[C];2006年

10 李菊香;萬磊;夏子榮;蘇海;顏素娟;程曉曙;吳清華;;細(xì)胞因子信號抑制物SOCS1/JAB介導(dǎo)CT-1對心肌胞急性缺氧復(fù)氧損傷的保護作用[A];江西省第四次中西醫(yī)結(jié)合心血管學(xué)術(shù)交流會論文集[C];2008年

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1 本報特約撰稿人 陸志城;SOCS3：抗過敏反應(yīng)藥物的新靶標(biāo)[N];醫(yī)藥經(jīng)濟報;2003年

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2 郭飛;GATA6上調(diào)LOXL2促進膽管癌侵襲轉(zhuǎn)移和FXR上調(diào)SOCS3抑制肝細(xì)胞癌增殖的研究[D];第三軍醫(yī)大學(xué);2015年

3 徐安濤;SOCS3促潰瘍性結(jié)腸炎腸道炎癥復(fù)發(fā)的機制研究[D];上海交通大學(xué);2015年

4 儲勤軍;SOCS3介導(dǎo)的IL6/STAT3炎癥通路在結(jié)直腸癌發(fā)生發(fā)展中的作用及機制研究[D];鄭州大學(xué);2016年

5 鄭君文;呼吸道合胞病毒非結(jié)構(gòu)蛋白和持續(xù)感染對SOCS1/3表達(dá)的影響[D];武漢大學(xué);2014年

6 夏子榮;SOCS3在心肌細(xì)胞缺氧復(fù)氧中的作用及調(diào)控機制[D];南昌大學(xué);2017年

7 徐召溪;調(diào)節(jié)PKC/NF-κB/SOCS3信號通路促進成年大鼠視神經(jīng)再生的研究[D];南方醫(yī)科大學(xué);2017年

8 周運恒;SOCS在原發(fā)性膽汁性肝硬化發(fā)病機制中的作用研究[D];第二軍醫(yī)大學(xué);2009年

9 邢長英;補腎益氣方調(diào)控人早孕滋養(yǎng)細(xì)胞SOCS3表達(dá)改善其生物學(xué)功能的研究[D];復(fù)旦大學(xué);2006年

10 張沛;SOCS3在心臟移植慢性排斥反應(yīng)中的作用和機制研究[D];華中科技大學(xué);2014年

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2 任倩;SOCS2和STAT5在喉癌中的表達(dá)及其臨床意義[D];山西醫(yī)科大學(xué);2015年

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5 徐旺;SOCS1介導(dǎo)AngⅡ促血管平滑肌細(xì)胞增殖的作用及機制[D];南昌大學(xué)醫(yī)學(xué)院;2015年

6 訾廣芹;過敏性紫癜兒童SOCS表達(dá)及與Th17/Treg細(xì)胞失衡關(guān)系研究[D];青島大學(xué);2015年

7 張慶群;SOCS低甲基化在過敏性紫癜兒童Th17/Treg細(xì)胞失衡中的作用研究[D];青島大學(xué);2015年

8 錢明;EGFR重組蛋白沖擊SOCS1沉默的DC對Hep-2細(xì)胞殺傷作用的研究[D];遼寧醫(yī)學(xué)院;2015年

9 桂博翔;SOCS3在H9N2禽流感病毒誘發(fā)急性肺損傷及繼發(fā)細(xì)菌性肺炎中的作用研究[D];華東師范大學(xué);2016年

10 郝連旭;半滑舌鰨CC型趨化因子和SOCS的系統(tǒng)發(fā)育和表達(dá)模式分析[D];中國科學(xué)院研究生院(海洋研究所);2016年

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