發(fā)布時(shí)間：2018-06-24 02:56

  本文選題：NLR家族 + TRPC離子通道　； 參考：《山東大學(xué)》2014年博士論文

【摘要】：研究目的：同型半胱氨酸是體內(nèi)甲硫氨酸循環(huán)的中間產(chǎn)物,其代謝異常所導(dǎo)致的高同型半胱氨酸血癥是終末期腎病(end stage renal disease, ESRD),以及心血管疾病并發(fā)癥導(dǎo)致的終末期腎病發(fā)生發(fā)展中的一個(gè)獨(dú)立危險(xiǎn)因子,但是高同型半胱氨酸所致腎損傷的發(fā)生發(fā)展機(jī)制迄今尚未完全明確。NOD2(nucleotide binding oligomerzation domain2)屬于模式識(shí)別受體(pattern-recognition receptors, PRRs)家族中的NLRs(NOD-1ike receptors, NLRs)亞家族成員,在免疫調(diào)控與炎性反應(yīng)中起著重要的作用,前期研究證實(shí)其在腎臟多種細(xì)胞中表達(dá)并且有實(shí)驗(yàn)證明小鼠NOD2缺失對(duì)腎臟缺血再灌注和糖尿病腎病中具有保護(hù)作用。TRPC6(transient receptor potential cation channe6, TRPC6)是具有鈣離子高選擇性的瞬時(shí)電位陽離子通道,作為足細(xì)胞裂孔膜的重要組成蛋白之一,其過度活化可致足細(xì)胞內(nèi)鈣離子濃度增高,從而導(dǎo)致足細(xì)胞損傷和功能障礙,引起腎小球疾病發(fā)生。但是,高同型半胱氨酸血癥中,NOD2是否參與了腎損傷的發(fā)生發(fā)展,及其是否與TRPC6存在調(diào)控關(guān)系并參與此病理過程,至今尚未見報(bào)道。為此,本課題分別從體內(nèi)和體外兩方面探討在高同型半胱酸血癥中,細(xì)胞內(nèi)固有免疫受體NOD2在腎小球硬化中的作用以及對(duì)TRPC6的調(diào)控機(jī)制,為防治高同型半胱氨酸癥導(dǎo)致的終末期腎病提供新的治療策略。 研究方法： 1.體內(nèi)實(shí)驗(yàn)：NOD2在高同型半胱氨酸血癥引起腎損傷中的作用及調(diào)控機(jī)制1.1高同型半胱氨酸血癥引起的小鼠腎損傷以及NOD2表達(dá)變化：實(shí)驗(yàn)采用健康成年雄性CBS+/-(strain name:B6.129P2-CbstmIUnc/J)小鼠和野生型雄性C57BL/6J小鼠。隨機(jī)分成四組,每組10只,野生型正常飲食組,野生型飲食葉酸缺乏組,CBS+／-小鼠正常飲食組和CBS+/-小鼠飲食葉酸缺乏組。高效液相色譜法(high performance liquid chromatography, HPLC)檢測(cè)各組血漿中總同型半胱氨酸含量,以評(píng)價(jià)模型是否復(fù)制成功；酶聯(lián)免疫吸附實(shí)驗(yàn)(enzyme-linked immunosorbent assay, ELISA)檢測(cè)尿白蛋白／肌酐水平；采用PAS染色觀察腎臟的形態(tài)學(xué)變化和電鏡觀察足細(xì)胞形態(tài)學(xué)變化；ELISA檢測(cè)相關(guān)致炎因子和趨化因子的水平。分別采用定量RT-PCR、蛋白免疫印跡法和免疫組織熒光化學(xué)法,檢測(cè)NOD2在小鼠腎皮質(zhì)以及腎小球足細(xì)胞中的表達(dá)變化。 1.2NOD2在高同型半胱氨酸血腎損傷中的作用及對(duì)TRPC6通道的調(diào)控機(jī)制研究：采用健康成年雄性NOD2-/-(strain name:B6.129S1-Nod2tmlFlv/J)小鼠和野生型雄性C57BL/6J小鼠,隨機(jī)分成四組,每組10只,野生型正常飲食組,野生型飲食葉酸缺乏組,NOD2-/-小鼠正常飲食組和NOD2-/-小鼠飲食葉酸缺乏組。采用免疫組化法觀察腎小球TRPC6和nephrin的表達(dá)；其他生化與形態(tài)指標(biāo),包括血漿總同型半胱氨酸含量、尿白蛋白肌酐水平、腎小球和足細(xì)胞的形態(tài)學(xué)變化、致炎因子和趨化因子在小鼠腎皮質(zhì)中的表達(dá)檢測(cè)及TRPC6和nephrin的表達(dá)檢測(cè)等,方法同上。 2.體外實(shí)驗(yàn)：NOD2對(duì)TRPC6通道的調(diào)控及小鼠足細(xì)胞損傷中的作用 體外培養(yǎng)腎小球上皮細(xì)胞(足細(xì)胞),并經(jīng)同型半胱氨酸刺激后,分別利用實(shí)時(shí)定量RT-PCR和蛋白免疫印跡法檢測(cè)足細(xì)胞中NOD2、TRPC6和nephrin的表達(dá)變化；MDP誘導(dǎo)足細(xì)胞內(nèi)NOD2活化,以及高同型半胱氨酸刺激轉(zhuǎn)染shRNA-NOD2質(zhì)粒獲得的NOD2基因沉默足細(xì)胞后,重復(fù)檢測(cè)上述指標(biāo)。采用流式細(xì)胞術(shù)分析上述各實(shí)驗(yàn)組中足細(xì)胞的凋亡情況,激光共聚焦觀察細(xì)胞骨架蛋白的結(jié)構(gòu)變化,鈣成像技術(shù)記錄足細(xì)胞內(nèi)鈣離子濃度的改變,全細(xì)胞膜片鉗技術(shù)分析TRPC6通道電流變化；為探討TRPC6和nephrin在信號(hào)路徑中的作用和相互關(guān)系,通過轉(zhuǎn)染shRNA-TRPC6質(zhì)�；虺聊慵�(xì)胞中的TRPC6,在同型半胱氨酸干預(yù)下,檢測(cè)細(xì)胞凋亡情況和骨架蛋白的結(jié)構(gòu)變化,質(zhì)粒轉(zhuǎn)染獲得過表達(dá)nephrin的足細(xì)胞,檢測(cè)其在Hcys刺激下TRPC6的蛋白表達(dá)水平的改變。 結(jié)果 1.體內(nèi)實(shí)驗(yàn)：NOD2在高同型半胱氨酸血癥引起的腎損傷中的作用及調(diào)控機(jī)制 1.1高同型半胱氨酸血癥引起的小鼠腎損傷以及NOD2表達(dá)變化： 首先,HPLC法檢測(cè)結(jié)果顯示野生葉酸缺乏組和CBS+／-葉酸缺乏組血漿總同型半胱氨酸水平均明顯高于正常飲食組(10μmol/L),表明高同型半胱氨酸血癥小鼠模型復(fù)制成功；尿白蛋白／肌酐比率與血漿總同型半胱氨酸水平呈正性相關(guān)；PAS染色可見正常飲食小鼠腎小球,基底膜清晰,粗細(xì)均勻,腎小球血管袢薄而清晰,而葉酸缺乏組小鼠腎小球均不同程度地呈現(xiàn)基底膜粗細(xì)不均,系膜增生,PAS陽性物質(zhì)沉積；通過電鏡觀察,足細(xì)胞超微結(jié)構(gòu)呈現(xiàn)基底膜厚薄不均,局部膨出,足細(xì)胞次級(jí)足突融合,CBS+／-葉酸缺乏組小鼠腎小球基底膜內(nèi)容物外漏,腎小球?yàn)V過屏障功能受損。以上結(jié)果表明,高同型半胱氨酸血癥引起了腎小球損傷。同時(shí),我們發(fā)現(xiàn)在高同型半胱氨酸血癥中,腎皮質(zhì)中小鼠NOD2蛋白和mRNA表達(dá)明顯增加；采用足細(xì)胞marker蛋白S ynaptopodin和NOD2共定位,免疫熒光共聚焦顯示高同型半胱氨酸血癥中,腎小球足細(xì)胞中NOD2蛋白高表達(dá)；并且小鼠腎皮質(zhì)白介素-1β(IL-1β).白介素-6(IL-6)、腫瘤壞死因子-α(TNF-α).單核細(xì)胞趨化蛋白-1(MCP-1).細(xì)胞間粘附分子-1(ICAM-1)的水平增高,表明高同型半胱氨酸血癥中腎皮質(zhì)的炎癥反應(yīng)增強(qiáng)。 1.2NOD2在高同型半胱氨酸血癥所致腎損傷中的作用及對(duì)TRPC6的調(diào)控機(jī)制研究： 血漿總同型半胱氨酸水平的檢測(cè)結(jié)果證實(shí),葉酸缺乏飲食復(fù)制高同型半胱氨酸血癥模型成功,雖然葉酸缺乏飲食導(dǎo)致NOD2-/-小鼠與野生小鼠的血漿tHcys無顯著性差異,但是NOD2基因敲除明顯降低了高同型半胱氨酸血癥中的尿白蛋白／肌酐比率,一定程度上緩解了小鼠腎功能障礙；形態(tài)學(xué)觀察結(jié)果表明NOD2基因敲除顯著減輕了高同型半胱氨酸血癥導(dǎo)致的腎小球損傷,并且發(fā)現(xiàn)腎小球基底膜膨出少見,足細(xì)胞次級(jí)足突排列較整齊,逆轉(zhuǎn)了高同型半胱氨酸血癥導(dǎo)致的小鼠腎小球足細(xì)胞損傷。我們進(jìn)一步發(fā)現(xiàn),高同型半胱氨酸血癥誘導(dǎo)小鼠腎小球TRPC6表達(dá)升高,而NOD2基因敲除能夠有效地抑制高同型半胱氨酸導(dǎo)致的TRPC6高表達(dá)和致炎因子以及趨化因子的產(chǎn)生；相反的,NOD2基因敲除一定程度上恢復(fù)了高同型半胱氨酸血癥所致的nephrin表達(dá)。上述結(jié)果說明,高同型半胱氨酸血癥導(dǎo)致的腎損傷過程中,NOD2參與了對(duì)TRPC6和nephrin的表達(dá)的調(diào)控。 2.體外實(shí)驗(yàn)：NOD2對(duì)TRPC6通道的調(diào)控及小鼠足細(xì)胞損傷中的作用 同型半胱氨酸誘導(dǎo)了體外培養(yǎng)足細(xì)胞中NOD2.TRPC6的表達(dá),導(dǎo)致OAG作用下的足細(xì)胞內(nèi)鈣濃度的增加,并且通過全細(xì)胞膜片鉗技術(shù)檢測(cè),發(fā)現(xiàn)TRPC6通道電流幅度的顯著升高。全細(xì)胞膜片鉗技術(shù)具有高靈敏度和高分辨率的特點(diǎn),電流可精確至1pA,空間和時(shí)間分辨率能達(dá)到1μm和10μs,實(shí)驗(yàn)采用特異性通道激動(dòng)劑OAG開放足細(xì)胞膜上TRPC6通道,記錄全細(xì)胞電流,能夠精確地反應(yīng)足細(xì)胞膜上TRPC6的通道數(shù)和開放概率。同樣,MDP活化足細(xì)胞NOD2后檢測(cè)到上述各指標(biāo)相同的變化趨勢(shì),而NOD2基因沉默后,同型半胱氨酸導(dǎo)致足細(xì)胞的上述變化被有效的抑制,表明同型半胱氨酸導(dǎo)致的足細(xì)胞TRPC6表達(dá)是NOD2依賴性的,并且NOD2參與調(diào)控同型半胱氨酸引起的TRPC6通道依賴性的鈣信號(hào)通路；激光共聚焦觀察進(jìn)一步發(fā)現(xiàn)NOD2活化和同型半胱氨酸均導(dǎo)致了足細(xì)胞骨架蛋白結(jié)構(gòu)重構(gòu),而TRPC6基因沉默與NOD2基因沉默結(jié)果一致性地改善了同型半胱氨酸導(dǎo)致的足細(xì)胞骨架重構(gòu),并且足細(xì)胞凋亡也明顯受到抑制；同時(shí),nephrin在足細(xì)胞中的表達(dá)由于NOD2活化或同型半胱氨酸被抑制,這與體內(nèi)實(shí)驗(yàn)中高同型半胱氨酸NOD2-/-小鼠腎皮質(zhì)nephrin水平高于其他實(shí)驗(yàn)組相呼應(yīng)；質(zhì)粒轉(zhuǎn)染獲得nephrin過表達(dá)的足細(xì)胞則有效降低了Hcys誘導(dǎo)的TRPC6的表達(dá)。結(jié)果證實(shí),NOD2介導(dǎo)的nephrin依賴性的TRPC6信號(hào)路徑參與了同型半胱氨酸引起的足細(xì)胞損傷過程。 結(jié)論與創(chuàng)新性： 1.本課題在高同型半胱氨酸血癥中,首次表明NOD2參與了對(duì)TRPC6離子通道的調(diào)控,提示TRPC6介導(dǎo)的鈣離子信號(hào)路徑是連接固有免疫受體NOD2和腎損傷的一條重要信號(hào)傳導(dǎo)途徑,針對(duì)NOD2信號(hào)路徑中各級(jí)分子的靶向治療有可能成為臨床防治高同型半胱氨酸血癥相關(guān)的終末期腎病的新的治療策略。 2.我們進(jìn)一步就NOD2調(diào)控TRPC6的機(jī)制及作用進(jìn)行深入研究,表明NOD2對(duì)nephrin的表達(dá)的調(diào)節(jié)可能是引起TRPC6變化的重要因素之一
[Abstract]:Objective : Homocysteine is an intermediate product of methionine circulation in vivo . The hyperhomocysteinemia caused by metabolic abnormalities is an independent risk factor in the development of renal ischemia reperfusion and diabetic nephropathy .

Study method :

1 . In vivo experiment : The effect of NOD2 in kidney injury induced by homocysteinemia and the expression of NOD2 in mice induced by hyperhomocysteinemia were studied . The experimental results showed that healthy adult male CBS + / - ( strain name : B6 . 129P2 - CbstmIUnc / J ) mice and wild - type male C57BL / 6J mice were randomly divided into four groups : 10 in each group , wild type normal diet group , wild type diet folic acid deficiency group , CBS + / - mouse normal diet group and CBS + / - mouse diet folic acid deficiency group .
Enzyme - linked immunosorbent assay ( ELISA ) was used to detect urinary albumin / creatinine levels .
The morphological changes of the kidney were observed by PAS staining and the morphological changes of the foot cells were observed by electron microscope .
Quantitative RT - PCR , Western blotting and immunohistochemistry were used to detect the expression of NOD2 in renal cortex of mice and glomerulus .

The effects of 1.2NOD2 on the renal injury of hyperhomocysteinemia and the control mechanism of TRPC6 pathway were studied : healthy adult male NOD2 - / - ( strain name : B6 . 129S1 - 2 tmlFlv / J ) mouse and wild - type male C57BL / 6J mice were randomly divided into four groups : 10 in each group , wild type normal diet group , wild type diet folic acid deficiency group , NOD2 - / - mouse normal diet group and NOD2 - / - mouse diet folic acid deficiency group .
Other biochemical and morphological indexes , including plasma total homocysteine levels , urinary albumin creatinine levels , morphological changes of glomerular and foot cells , inflammatory factors and chemokine expression in renal cortex of mice , and expression of TRPC6 and nephrin .

2 . In vitro experiment : The effect of NOD2 on TRPC6 channel regulation and mouse foot cell injury

The expression of NOD2 , TRPC6 and nephrin was detected by real - time quantitative RT - PCR and Western blotting respectively after the cultured glomerular epithelial cells ( foot cells ) were cultured in vitro and stimulated with homocysteine .
The expression of NOD2 gene was detected by flow cytometry . The changes of calcium ion concentration in the cells were observed by flow cytometry , and the changes of calcium ion concentration in the cells were recorded by calcium imaging technique .
In order to investigate the role and correlation of TRPC6 and nephrin in signal path , TRPC6 was transfected with shRNA - TRPC6 plasmid gene to silence TRPC6 . Under the intervention of homocysteine , the apoptosis of cells and the structural changes of skeletal proteins were detected . The expression level of TRPC6 was detected by plasmid transfection .

Results

1 . In vivo experiment : The effect and mechanism of NOD2 in renal injury induced by homocysteinemia

1.1 Changes in renal impairment and NOD2 expression in mice due to hyperhomocysteinemia :

First , the levels of plasma total homocysteine in the wild folate deficiency group and CBS + / - folate deficiency group were significantly higher than those in the normal diet group ( 10 渭mol / L ) .
Urinary albumin / creatinine ratio was positively correlated with the level of plasma homocysteine ;
PAS staining showed that the glomeruli of normal diet mice , the basement membrane was clear , the thickness was uniform , the glomerulus vascular loop was thin and clear , and the glomerulus of the folic acid deficient group presented the basement membrane coarse and fine unevenness , mesangial hyperplasia and PAS positive substance deposition .
The results showed that the expression of NOD2 protein and mRNA in renal cortex was significantly increased in hyperhomocysteinemia .
The high expression of NOD2 protein in hyperhomocysteinemia was demonstrated by co - localization of the foot cell marker protein S ynaptopodin and NOD2 .
IL - 1尾 ( IL - 1尾 ) , interleukin - 6 ( IL - 6 ) , tumor necrosis factor - 偽 ( TNF - 偽 ) , monocyte chemoattractant protein - 1 ( MCP - 1 ) . The level of intercellular adhesion molecule - 1 ( ICAM - 1 ) increased .

The role of 1.2NOD2 in renal injury induced by homocysteinemia and its mechanism of regulation of TRPC6 :

The result of detection of plasma total homocysteine level confirmed that folate deficiency diet induced the success of hyperhomocysteinemia model , although folate deficiency diet resulted in no significant difference between NOD2 - / - mice and wild mice , but NOD2 knockout significantly reduced urinary albumin / creatinine ratio in hyperhomocysteinemia , to a certain extent the impairment of renal dysfunction in mice ;
The results of morphological observation showed that the knock - out of NOD2 gene significantly alleviated the glomerular injury caused by hyperhomocysteinemia , and it was found that the expression of TRPC6 in mice induced by homocysteinemia was reversed , while the NOD2 gene knocked out the high expression of TRPC6 induced by homocysteinemia and the production of inflammatory factor and chemokine .
In contrast , the NOD2 gene knockout to some extent restores nephrin expression resulting from hyperhomocysteinemia . The above results suggest that NOD2 is involved in regulating the expression of TRPC6 and nephrin in the course of renal injury resulting from hyperhomocysteinemia .

2 . In vitro experiment : The effect of NOD2 on TRPC6 channel regulation and mouse foot cell injury

The expression of NOD2 and TRPC6 was induced by homocysteine , which resulted in the increase of intracellular calcium concentration in the cells under the action of OAG , and it was found that TRPC6 channel current amplitude was significantly increased by whole cell patch clamp technique .
Laser cofocus observation further found that both NOD2 activation and homocysteine resulted in the structural remodeling of the scaffold protein of the foot cells , while the silencing of TRPC6 gene and the silencing of NOD2 gene significantly improved the remodeling of the foot cytoskeletal structure caused by homocysteine , and the apoptosis of the foot cells was also significantly inhibited ;
At the same time , the expression of nephrin in full - term cells was inhibited by NOD2 activation or homocysteine , which was correlated with the level of nephrin in renal cortex of high homocysteine NOD2 - / - mice in vivo experiments than in other experimental groups ;
The results showed that the TRPC6 signal pathway mediated by NOD2 mediated nephrin - dependent TRPC6 signal pathway was involved in the process of foot cell injury induced by homocysteine .

Conclusion and Innovation :

1 . In hyperhomocysteinemia , NOD2 is shown to be involved in the regulation of TRPC6 ion channel . It is suggested that TRPC6 - mediated calcium ion signal pathway is an important signal transduction pathway linking innate immune receptor NOD2 and kidney injury . Targeting therapy for all levels of NOD2 signaling pathway may be a new treatment strategy for the treatment of end - stage renal disease associated with hyperhomocysteinemia .

2 . We further study the mechanism and function of NOD2 regulation TRPC6 , indicating that the regulation of NOD2 ' s expression of nephrin may be one of the important factors that cause TRPC6 change
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R692.5;R589

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 魏銘;徐德生;;縫隙連接在伽瑪?shù)端路派鋼p傷中的作用[J];國(guó)際神經(jīng)病學(xué)神經(jīng)外科學(xué)雜志;2008年03期

2 隗黎麗;吳華東;熊六鳳;;柱狀黃桿菌對(duì)草魚TLRs基因表達(dá)水平的影響[J];大連海洋大學(xué)學(xué)報(bào);2013年04期

3 胡堅(jiān);楊閏平;汶春苗;李恒進(jìn);趙華;;NLRP3炎癥小體在咪喹莫特誘導(dǎo)小鼠銀屑病樣模型中的表達(dá)及芥菜籽對(duì)其的影響[J];南方醫(yī)科大學(xué)學(xué)報(bào);2013年09期

4 廖萌;嚴(yán)孫杰;;成骨細(xì)胞Toll樣受體4信號(hào)通路研究進(jìn)展[J];中華骨質(zhì)疏松和骨礦鹽疾病雜志;2013年03期

5 李致宏;馬振剛;李晚軍;劉軍;韓冰;李田;潘國(guó)慶;李春峰;周澤揚(yáng);;感染家蠶微孢子蟲的蠶體血淋巴蛋白質(zhì)差異表達(dá)分析及質(zhì)譜鑒定[J];蠶業(yè)科學(xué);2013年05期

6 李鵬;夏琳;扈英偉;徐欣;;免疫反應(yīng)在牙周病牙槽骨吸收中的作用[J];北京口腔醫(yī)學(xué);2013年05期

7 余夢(mèng)辰;李斌;周紅;;內(nèi)毒素識(shí)別、內(nèi)化及清除相關(guān)受體的研究進(jìn)展[J];重慶醫(yī)學(xué);2013年29期

8 姜瀾;宋智;林正梅;;核苷酸結(jié)合寡聚化結(jié)構(gòu)域蛋白及其在牙髓中的表達(dá)[J];國(guó)際口腔醫(yī)學(xué)雜志;2013年05期

9 劉爭(zhēng)輝;韓代書;;模式識(shí)別受體介導(dǎo)的天然免疫反應(yīng)調(diào)節(jié)獲得性免疫的機(jī)理[J];中國(guó)組織化學(xué)與細(xì)胞化學(xué)雜志;2013年06期

10 瞿全新;糜若然;;TLR3在宮頸抗病毒免疫及宮頸病變中的作用[J];國(guó)際婦產(chǎn)科學(xué)雜志;2013年06期

相關(guān)會(huì)議論文 前1條

1 Wei Long;Jinhang Zan;Zewei Zhou;Xin He;Jin Jin;Saijun Fan;Peixun Liu;;Computational Simulation for Binding Interaction of TLR5 with Flagellin[A];第二屆國(guó)際計(jì)算科學(xué)與工程國(guó)際學(xué)術(shù)研討會(huì)論文集[C];2013年

相關(guān)博士學(xué)位論文 前10條

1 曾暢;TRPC3、TRPC6通道對(duì)顳葉癲癇小鼠癇性發(fā)作及海馬神經(jīng)元可塑性的調(diào)控[D];中南大學(xué);2011年

2 孫玉;Caveolin-1在氧化應(yīng)激致肺血管通透性增加中的作用和調(diào)控機(jī)制[D];山東大學(xué);2010年

3 湯喜蘭;廣棗抗心肌缺血再灌注損傷的物質(zhì)基礎(chǔ)及作用機(jī)制研究[D];北京中醫(yī)藥大學(xué);2013年

4 趙一萍;蒙古馬免疫相關(guān)基因表達(dá)研究及脾臟表達(dá)譜分析[D];內(nèi)蒙古農(nóng)業(yè)大學(xué);2013年

5 薛雪;AQP4基因缺失對(duì)中腦TGF-β產(chǎn)生的影響及其與帕金森疾病的相關(guān)研究[D];南京醫(yī)科大學(xué);2013年

6 王晶晶;中華絨螯蟹免疫致敏現(xiàn)象及相關(guān)分子機(jī)制的初步研究[D];中國(guó)科學(xué)院研究生院（海洋研究所）;2013年

7 王雷雷;扇貝補(bǔ)體相關(guān)分子的結(jié)構(gòu)及功能研究[D];中國(guó)科學(xué)院研究生院（海洋研究所）;2013年

8 趙敏;高脂飲食對(duì)大鼠肝臟內(nèi)質(zhì)網(wǎng)應(yīng)激和炎癥的影響及低脂膳食干預(yù)效果研究[D];華中科技大學(xué);2013年

9 畢麗麗;豬溶素誘導(dǎo)宿主產(chǎn)生炎癥因子的分子機(jī)制研究[D];中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院;2013年

10 趙殿元;DC上表達(dá)的LSECtin對(duì)輔助性T細(xì)胞亞群分化的影響及其機(jī)制研究[D];中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院;2013年

相關(guān)碩士學(xué)位論文 前10條

1 魏銘;伽瑪?shù)墩丈浼凹讖?qiáng)龍治療對(duì)膠質(zhì)細(xì)胞CX43及GFAP表達(dá)的影響[D];天津醫(yī)科大學(xué);2009年

2 楊黎;高糖及胰島素對(duì)腎小管上皮細(xì)胞通透性及Connexin43表達(dá)的影響[D];重慶醫(yī)科大學(xué);2009年

3 趙達(dá);鼠傷寒沙門氏菌鞭毛蛋白對(duì)牛金黃色葡萄球菌GapC蛋白的免疫增強(qiáng)作用[D];黑龍江八一農(nóng)墾大學(xué);2013年

4 張弘韜;轉(zhuǎn)TLR2基因綿羊鑒定及其炎癥反應(yīng)研究[D];黑龍江八一農(nóng)墾大學(xué);2013年

5 徐漢陽;擬南芥EFR與黑腹果蠅SCOT蛋白重組表達(dá)、純化及晶體研究[D];安徽大學(xué);2013年

6 白雪;柚皮素對(duì)大鼠局灶性腦缺血損傷的保護(hù)作用及對(duì)NOD2、RIP2、NF-κB、MMP-9和claudin-5表達(dá)影響的研究[D];河北醫(yī)科大學(xué);2013年

7 喬紅秀;病毒及質(zhì)粒DNA刺激后小鼠肌細(xì)胞內(nèi)IFN-β與PD-L1的表達(dá)情況[D];河北醫(yī)科大學(xué);2013年

8 吳翠紅;PM_(2.5)急性暴露對(duì)博來霉素致大鼠肺纖維化的影響及機(jī)制[D];河北醫(yī)科大學(xué);2013年

9 李元;不同急性肝損傷模型大鼠卵圓細(xì)胞生物學(xué)差異及自噬的變化[D];河北醫(yī)科大學(xué);2013年

10 殷小磊;布拉氏酵母菌對(duì)實(shí)驗(yàn)性大鼠非酒精性脂肪性肝炎的療效及其作用機(jī)制的研究[D];河北醫(yī)科大學(xué);2013年

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