本文選題：腦出血 + 血腫吸收�。� 參考：《第三軍醫(yī)大學(xué)》2014年博士論文

【摘要】：腦出血(intracerebralhemorrhage,ICH)是一種常見的中風(fēng)類型，雖經(jīng)多年研究，但至今治療手段有限。在動(dòng)物實(shí)驗(yàn)及臨床實(shí)踐中發(fā)現(xiàn)，ICH后腦組織自身具有血腫吸收清除的能力，而且患者臨床結(jié)局的好壞與血腫吸收速度的快慢呈明顯正相關(guān)。因此促進(jìn)內(nèi)源性血腫吸收成為治療ICH的新途徑。 ICH后血腫成分可導(dǎo)致小膠質(zhì)細(xì)胞激活。在ICH早期，小膠質(zhì)細(xì)胞可以通過吞噬紅細(xì)胞及紅細(xì)胞溶解成份來(lái)清除血腫。小膠質(zhì)細(xì)胞發(fā)揮吞噬功能主要由清道夫受體CD36介導(dǎo)。CD36參與了小膠質(zhì)細(xì)胞吞噬β-淀粉樣蛋白、氧化低密度脂蛋白過程，并引起慢性無(wú)菌炎癥，在阿爾茨海默氏病、動(dòng)脈粥樣硬化的發(fā)病中起作用。但CD36在ICH后的表達(dá)及其作用尚未闡明。 越來(lái)越多的證據(jù)表明，炎癥是ICH引起繼發(fā)性腦損傷的關(guān)鍵因素。研究顯示TLR4參與了無(wú)菌性炎癥的發(fā)生發(fā)展，在中樞神經(jīng)系統(tǒng)炎癥反應(yīng)中具有重要地位。已有研究顯示TLR4信號(hào)激活產(chǎn)生的TNF-α等炎癥因子可以下調(diào)巨噬細(xì)胞上的CD36的表達(dá)，進(jìn)而影響巨噬細(xì)胞吞噬功能。但在ICH過程中，TLR4信號(hào)能否調(diào)控小膠質(zhì)細(xì)胞的CD36表達(dá)，并進(jìn)而影響吞噬功能尚不清楚。 在本研究中，我們首先利用臨床ICH病例，觀察了CD36缺陷患者血腫吸收及神經(jīng)功能恢復(fù)情況。在此基礎(chǔ)上，利用在體和離體ICH模型，觀察了CD36在ICH后表達(dá)變化規(guī)律及其在血腫吸收中的作用；然后我們觀察了TLR4信號(hào)通路對(duì)CD36表達(dá)的調(diào)控及其對(duì)小膠質(zhì)細(xì)胞吞噬功能的影響，探討了ICH后CD36調(diào)控血腫吸收的相關(guān)機(jī)制。最后觀察了TLR4抑制劑TAK242對(duì)CD36表達(dá)的調(diào)控及其對(duì)小膠質(zhì)細(xì)胞吞噬作用的影響。 第一部分CD36缺陷對(duì)腦出血患者血腫吸收及神經(jīng)功能缺損的影響 目的：觀察CD36缺陷腦出血患者血腫吸收變化和相應(yīng)神經(jīng)功能恢復(fù)情況，以明確腦出血過程中CD36的功能。 方法：收集199例腦出血患者一般臨床及頭顱CT資料，并對(duì)患者進(jìn)行NIHHS評(píng)分和mRS評(píng)分。利用PCR-SSP技術(shù)和Western blot技術(shù)對(duì)患者進(jìn)行CD36缺陷篩查和分型鑒定，篩查出CD36Ⅰ型缺陷患者做為CD36缺陷組。同時(shí)挑選出具有和CD36缺陷組相同部位、相同出血量的CD36正�；颊咦鳛檎�(duì)照組。對(duì)比兩組患者的腦出血后血腫吸收速度和相應(yīng)神經(jīng)功能評(píng)分。 結(jié)果：我們共篩查18例CD36缺陷患者(9.0%)，其中11例為CD36I型缺陷(5.5%)。與對(duì)照組相比，CD36缺陷患者入院時(shí)臨床基本資料、影像學(xué)特征、生化指標(biāo)無(wú)顯著差異，但經(jīng)過相同治療后，CD36缺陷患者血腫吸收速度顯著減慢，NIHSS評(píng)分及mRS評(píng)分顯著增高。 結(jié)論：CD36缺陷患者血腫吸收減慢，神經(jīng)功能缺損評(píng)分加重，提示CD36參與了血腫吸收，并與神經(jīng)功能的恢復(fù)相關(guān)。 第二部分，CD36在腦出血后腦組織中表達(dá)及其在血腫吸收中的作用 目的：觀察腦出血后腦細(xì)胞CD36表達(dá)及其變化；了解CD36缺陷后血腫吸收及小膠質(zhì)細(xì)胞吞噬能力的變化，從而明確CD36在血腫吸收過程中的作用； 方法：首先采用小鼠在體腦出血模型，利用Real-time RT-PCR、Western Blot觀察腦出血后CD36表達(dá)的變化；其次利用免疫熒光化學(xué)等方法，觀察人和小鼠腦出血后CD36主要在哪種腦細(xì)胞表達(dá)；再次利用離體腦出血模型，通過流式細(xì)胞儀、免疫熒光染色，觀察CD36-/-小膠質(zhì)細(xì)胞吞噬能力的變化，最后采用在體腦出血模型，觀察CD36-/-小鼠血腫吸收和神經(jīng)功能缺損等變化，以進(jìn)一步證實(shí)CD36在腦出血血腫吸收中的作用。 結(jié)果：與Sham組相比，腦出血組第1天CD36表達(dá)就有顯著差異，到第3天達(dá)到高峰，到第7天CD36表達(dá)仍維持較高水平。CD36可以在神經(jīng)元細(xì)胞、星型膠質(zhì)細(xì)胞、小膠質(zhì)細(xì)胞上表達(dá)，但以小膠質(zhì)細(xì)胞表達(dá)為主。小膠質(zhì)細(xì)胞可以直接吞噬紅細(xì)胞，并且CD36-/-小膠質(zhì)細(xì)胞或使用CD36抗體封閉的小膠質(zhì)細(xì)胞吞噬紅細(xì)胞的能力顯著減弱。與野生型小鼠相比，CD36-/-鼠腦出血后血腫吸收顯著減慢，神經(jīng)功能恢復(fù)顯著減慢，TNF-α、IL-1β表達(dá)顯著增多。 結(jié)論：1. CD36在腦出血后表達(dá)顯著增高，，在第3天達(dá)到最高峰，在第7天仍維持較高水平的表達(dá)，提示CD36參與了腦出血的病理過程。而且腦出血后，CD36主要在小膠質(zhì)細(xì)胞表達(dá)。 2. CD36-/-小膠質(zhì)細(xì)胞對(duì)紅細(xì)胞吞噬能力降低，使用CD36抗體封閉野生型小膠質(zhì)細(xì)胞也得到類似結(jié)果，提示CD36在小膠質(zhì)吞噬RBC過程中起十分重要作用。 3. CD36-/-鼠腦出血后血腫吸收減慢，神經(jīng)功能缺損加重，腦含水量增多，TNF-α/IL-1β等炎癥因子分泌增多，提示CD36參與了血腫吸收，并與神經(jīng)功能的預(yù)后相關(guān)。提示CD36可以作為治療腦出血的一個(gè)新靶點(diǎn)。 第三部分TLR4信號(hào)激活并負(fù)調(diào)控CD36表達(dá)影響腦出血血腫吸收及機(jī)制 目的：觀察TLR4-/-、MyD88-/-鼠腦出血后CD36表達(dá)變化，同時(shí)觀察TLR4信號(hào)通路對(duì)血腫吸收和對(duì)小膠質(zhì)細(xì)胞吞噬紅細(xì)胞能力的影響，進(jìn)而研究TLR4信號(hào)通路對(duì)CD36表達(dá)調(diào)控的機(jī)制。 方法：使用在體腦出血模型，用Western blot檢測(cè)TLR4-/-、MyD88-/-鼠腦出血后CD36表達(dá)，并觀察TLR4-/-、MyD88-/-鼠血腫吸收情況；使用離體腦出血模型，用流式細(xì)胞儀檢測(cè)TLR4-/-、MyD88-/-小膠質(zhì)細(xì)胞CD36表達(dá)和吞噬能力的變化；利用離體腦出血模型，用Western blot和流式細(xì)胞儀觀察炎癥因子對(duì)小膠質(zhì)細(xì)胞CD36表達(dá)和吞噬能力的影響。 結(jié)果：與野生型小鼠相比，TLR4-/-、MyD88-/-鼠腦出血后CD36表達(dá)顯著增高，血腫吸收顯著增快。與野生型小膠質(zhì)細(xì)胞相比，TLR4-/-、MyD88-/-小膠質(zhì)細(xì)胞CD36表達(dá)顯著增加，吞噬能力增強(qiáng)，而且這種作用可以被CD36抗體阻斷。TLR4信號(hào)通路下游主要炎癥因子TNF-α、IL-1β可以抑制小膠質(zhì)細(xì)胞CD36表達(dá)，減弱其吞噬能力，TNF-α作用更加明顯。 結(jié)論：1. TLR4-/-、MyD88-/-鼠腦出血后CD36表達(dá)增高，血腫吸收增快，提示TLR4信號(hào)途徑參與CD36表達(dá)的調(diào)控。 2.在離體腦出血模型中,TLR4-/-、MyD88-/-小膠質(zhì)細(xì)胞CD36表達(dá)增高，吞噬紅細(xì)胞能力增強(qiáng)。而使用CD36抗體后，可以減弱該作用，進(jìn)一步證實(shí)TLR4信號(hào)途徑參與CD36表達(dá)的調(diào)控。 3.在離體腦出血模型中，TLR4信號(hào)通路下游炎癥因子TNF-α、IL-1β可以抑制小膠質(zhì)細(xì)胞的CD36表達(dá)，并且可以削弱小膠質(zhì)細(xì)胞的吞噬能力，其中以TNF-α為主，提示TLR4信號(hào)通路通過TNF-α、IL-1β負(fù)調(diào)控CD36的表達(dá)。 第四部分TLR4抑制劑促進(jìn)CD36表達(dá)，影響腦出血血腫吸收 目的：觀察TLR4抑制劑TAK242對(duì)小膠質(zhì)細(xì)胞CD36表達(dá)和吞噬能力的影響，觀察TAK242對(duì)神經(jīng)元的保護(hù)作用及可能機(jī)制。觀察TAK242對(duì)小鼠腦出血后血腫吸收的影響。 方法：使用離體腦出血模型，用Western blot和流式細(xì)胞儀檢測(cè)TAK242對(duì)小膠質(zhì)細(xì)胞CD36表達(dá)和吞噬能力的影響；利用神經(jīng)元、小膠質(zhì)細(xì)胞共培養(yǎng)技術(shù)，觀察TAK242對(duì)神經(jīng)元的保護(hù)作用；在離體腦出血模型中，用Real-time RT-PCR檢測(cè)TAK242對(duì)過氧化氫酶表達(dá)的影響，并測(cè)定過氧化氫濃度；同時(shí)使用在體腦出血模型，并觀察TAK242對(duì)血腫吸收的影響。 結(jié)果：在離體腦出血模型中，與對(duì)照組相比，TAK242增加了小膠質(zhì)細(xì)胞CD36表達(dá)和吞噬能力，而炎癥因子TNF-α、IL-1β可以減弱TAK242這一作用；在神經(jīng)元、小膠質(zhì)細(xì)胞共培養(yǎng)體系中，TAK242顯著減少了神經(jīng)元凋亡/壞死數(shù)量，并且增加了小膠質(zhì)細(xì)胞的過氧化氫酶表達(dá)，減少過氧化氫分泌；在小鼠腦出血模型中，與對(duì)照組相比，TAK242可以促進(jìn)腦出血血腫的吸收。 結(jié)論：1.TAK242可以增強(qiáng)小膠質(zhì)細(xì)胞CD36表達(dá)和吞噬紅細(xì)胞能力，而TNF-α和IL-1β可以減弱TAK242作用，證明TAK242是通過抑制TLR4信號(hào)通路進(jìn)而影響CD36表達(dá)。 2. TAK242增加小膠質(zhì)細(xì)胞的過氧化氫酶表達(dá)，減少過氧化氫分泌，對(duì)神經(jīng)元細(xì)胞具有保護(hù)作用。 3. TAK242不僅具有神經(jīng)保護(hù)作用，而且促進(jìn)了血腫的吸收，可能成為治療腦出血的新藥物。 本研究在觀察CD36在腦出血血腫吸收中作用的基礎(chǔ)上，同時(shí)探討了TLR4信號(hào)調(diào)控CD36表達(dá),進(jìn)而影響血腫吸收。進(jìn)一步明確了腦出血血腫吸收的調(diào)控機(jī)制，也為通過促進(jìn)血腫吸收治療ICH這一全新理念提供實(shí)驗(yàn)依據(jù)，可望為ICH治療提供新方法。
[Abstract]:Cerebral hemorrhage ( ICH ) is a common type of stroke . Although it has been studied for many years , the treatment has been limited . In animal experiments and clinical practice , it has been found that the brain tissue itself has the ability to absorb and remove hematoma , and the clinical outcome of the patient is positively correlated with the fast and slow speed of hematoma absorption . Therefore , it is a new way to promote the absorption of endogenous hematoma .

2 . CD36 - / - microglial cells decreased the phagocytosis of erythrocytes . Similar results were obtained by using CD36 antibody to close wild - type microglial cells , suggesting that CD36 plays an important role in the RBC process .

More and more evidence shows that inflammation is a key factor in ICH - induced secondary brain injury . The study shows that it is involved in the development of aseptic inflammation and plays an important role in the inflammatory response of the central nervous system .

In this study , we first used the clinical ICH cases to observe the absorption of hematoma and the recovery of neurological function in patients with CD36 deficiency . On the basis of this , the change rule of CD36 in ICH and its role in the absorption of hematoma were observed by using in vivo and ex vivo ICH models .
Then we observed the regulation of the expression of CD36 and its influence on the phagocytic function of microglial cells , and discussed the mechanism of CD36 - regulated hematoma absorption after ICH . Finally , the regulation of CD36 expression and its effect on the phagocytosis of CD36 were observed .

The effect of CD36 deficiency on hematoma absorption and neurological deficit in patients with cerebral hemorrhage

Objective : To observe the changes of hematoma absorption and the recovery of corresponding neurological function in patients with cerebral hemorrhage of CD36 , so as to clarify the function of CD36 in the course of cerebral hemorrhage .

Methods : 199 patients with cerebral hemorrhage were collected from clinical and skull CT data and NIHHS and mRS were scored . CD36 patients were identified by PCR - SSP and Western blot .

Results : We screened 18 patients with CD36 deficiency ( 9.0 % ) , 11 of them were CD36 I defect ( 5.5 % ) . Compared with the control group , the clinical basic data , imaging characteristics and biochemical indexes were not significantly different in patients with CD36 deficiency , but after the same treatment , the absorption rate of hematoma in patients with CD36 was significantly decreased , NIHSS score and mRS score were significantly increased .

Conclusion : The absorption of hematoma in patients with CD36 deficiency is slow and the score of neurological deficit is aggravated , suggesting that CD36 is involved in the absorption of hematoma and is related to the recovery of neurological function .

The second part , the expression of CD36 in brain tissue after intracerebral hemorrhage and its role in the absorption of hematoma

Objective : To observe the expression of CD36 and its changes in brain cells after intracerebral hemorrhage .
To understand the changes of the absorption of hematoma and the phagocytic ability of microglial cells after CD36 defects , so as to clarify the role of CD36 in the absorption of hematoma ;


Methods : The expression of CD36 in intracerebral hemorrhage was observed by Real - time RT - PCR and Western Blot .
Secondly , the expression of CD36 was observed in the brain cells of human and mouse after intracerebral hemorrhage by immunofluorescence chemistry .
The changes of the phagocytic ability of CD36 - / - microglial cells were observed by flow cytometry and immunofluorescence staining , and the changes of CD36 - / - mouse hematoma absorption and neurological deficit were observed by flow cytometry and immunofluorescence staining to further confirm the role of CD36 in the absorption of hematoma hematoma .

Results : Compared with the Sham group , the expression of CD36 in the first day of the cerebral hemorrhage group was significantly different , and the expression of CD36 on the 7th day was still higher than that in the wild type mice .

Conclusion : 1 . CD36 expression increased significantly after intracerebral hemorrhage , reached the highest peak on Day 3 , and maintained a high level of expression on Day 7 , suggesting that CD36 was involved in the pathological process of cerebral hemorrhage . After intracerebral hemorrhage , CD36 was mainly expressed in microglial cells .

In the early ICH , microglial cells can remove hematoma by phagocytizing red blood cells and red blood cell lysis components . CD36 plays a role in the phagocytosis of 尾 - amyloid , oxidized low - density lipoprotein , and causes chronic aseptic inflammation , plays a role in the pathogenesis of Alzheimer ' s disease and atherosclerosis . However , the expression of CD36 after ICH and its role have not yet been clarified .

Conclusion CD36 can be used as a new target for the treatment of cerebral hemorrhage .

The signal activation and negative regulation of CD36 expression in the third part affect the absorption and mechanism of hematoma hematoma .

Objective : To observe the changes of CD36 expression after intracerebral hemorrhage in mice after intracerebral hemorrhage , and observe the effect of the signal pathway on the absorption of hematoma and the ability to phagocytize the red blood cell of microglial cells .

Methods : Using the model of intracerebral hemorrhage , Western blot was used to detect the expression of CD36 after intracerebral hemorrhage , and observe the absorption of CD36 - / - , MyD88 - / - mouse hematoma .
Using isolated intracerebral hemorrhage model , the expression of CD36 and the phagocytic ability were detected by flow cytometry .
The effects of inflammatory factors on CD36 expression and phagocytic ability of microglial cells were observed by Western blot and flow cytometry .

Results : Compared with wild type mice , the expression of CD36 was significantly increased after intracerebral hemorrhage , and the absorption of hematoma was increased significantly . Compared with wild type microglial cells , the expression of CD36 was increased and the phagocytic ability was enhanced . The main inflammatory factors TNF - 偽 and IL - 1尾 downstream of the signal pathway could inhibit the expression of CD36 in microglial cells , weaken its phagocytic ability and play a more obvious role in TNF - 偽 .

Conclusion : 1 . After intracerebral hemorrhage , the expression of CD36 increased after intracerebral hemorrhage , and the absorption of hematoma increased rapidly , suggesting that the signal pathway involved in the regulation of CD36 expression .

2 . In the model of ex vivo cerebral hemorrhage , the expression of CD36 , the expression of CD36 and the ability of phagocytosis increased . After using CD36 antibody , the function could be weakened , and the pathway involved in the regulation of CD36 expression was further confirmed .

3 . In the model of isolated intracerebral hemorrhage , the downstream inflammatory cytokines TNF - 偽 and IL - 1尾 can inhibit the expression of CD36 in microglial cells , and the phagocytic ability of microglial cells can be weakened . The expression of TNF - 偽 and IL - 1尾 negatively regulates the expression of CD36 through TNF - 偽 and IL - 1尾 .

Fourthly , the expression of CD36 and the absorption of CD36 in cerebral hemorrhage were affected .

Objective : To observe the effect of TAK242 inhibitor TAK242 on the expression and phagocytic ability of CD36 in mice , and observe the protective effect and possible mechanism of TAK242 on neurons .

Methods : The effect of TAK242 on CD36 expression and phagocytic ability of microglial cells was detected by Western blot and flow cytometry using isolated intracerebral hemorrhage model .
The protective effect of TAK242 on neurons was observed by co - culture with neurons and microglial cells .
In vitro cerebral hemorrhage model , the effect of TAK242 on catalase expression was detected by Real - time RT - PCR , and the concentration of hydrogen peroxide was measured .
The effect of TAK242 on hematoma absorption was observed .

Results : Compared with the control group , TAK242 increased the expression and phagocytic ability of CD36 in microglial cells compared with the control group , while the inflammatory factors TNF - 偽 and IL - 1尾 could attenuate the role of TAK242 .
In the co - culture system of neurons and microglial cells , TAK242 significantly reduces the number of neuron apoptosis / necrosis and increases the expression of catalase in microglial cells and reduces the secretion of hydrogen peroxide ;
Compared with the control group , TAK242 can promote the absorption of hematoma in intracerebral hemorrhage .

Conclusion : 1 . TAK242 can enhance the expression of CD36 in microglial cells and the ability of phagocytizing red blood cells , and TNF - 偽 and IL - 1尾 can attenuate the role of TAK242 , which proves that TAK242 can inhibit the expression of CD36 by inhibiting the signaling pathway .

2 . TAK242 increases the expression of catalase in microglial cells , reduces the secretion of hydrogen peroxide , and has protective effect on neuronal cells .

3 . TAK242 has not only nerve protection , but also promotes the absorption of hematoma , which may become a new drug for the treatment of cerebral hemorrhage .

Based on the observation of the role of CD36 in the absorption of hematoma in intracerebral hemorrhage , the expression of CD36 and the absorption of the hematoma were discussed . The mechanism of the absorption of hematoma was further clarified , and the experimental basis was provided for the new idea of promoting the absorption of hematoma , which could provide a new method for ICH therapy .

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.34

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 賀曉生;費(fèi)舟;;Toll樣受體在創(chuàng)傷性腦損傷中的作用與調(diào)控研究[J];創(chuàng)傷外科雜志;2009年04期

2 楊策;陳永華;黃宏;王海燕;謝國(guó)旗;蔣建新;;創(chuàng)傷感染時(shí)巨噬細(xì)胞表面模式識(shí)別受體表達(dá)、相互作用及其與炎癥反應(yīng)發(fā)生的關(guān)系[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2009年15期

3 潘新發(fā);萬(wàn)曙;詹仁雅;;腦出血后血腫周圍組織炎癥反應(yīng)的研究進(jìn)展[J];國(guó)際神經(jīng)病學(xué)神經(jīng)外科學(xué)雜志;2010年03期

4 王超;路華;楊智勇;;TLR4信號(hào)通路在腦卒中后腦損傷中的研究進(jìn)展[J];國(guó)際神經(jīng)病學(xué)神經(jīng)外科學(xué)雜志;2010年06期

5 龔雪琴;;針灸治療腦出血的循證醫(yī)學(xué)評(píng)價(jià)[J];成都中醫(yī)藥大學(xué)學(xué)報(bào);2013年03期

6 徐洪兵;何二平;王福林;劉昊;徐紅青;呂愛華;;高血壓腦出血治療方法的選擇(附248例報(bào)告)[J];北方藥學(xué);2013年11期

7 敏思聰;俞銀賢;馬金忠;;TLR4信號(hào)轉(zhuǎn)導(dǎo)通路與骨關(guān)節(jié)炎[J];國(guó)際骨科學(xué)雜志;2013年04期

8 Arun Kumar;;Biomedical studies on lipid peroxidation and erythrocyte fragility during the process of aging[J];Asian Pacific Journal of Tropical Biomedicine;2011年01期

9 余永程;楊華榮;鄭江環(huán);寧麗潔;伍國(guó)鋒;;微創(chuàng)治療與藥物治療高血壓腦出血的臨床分析[J];重慶醫(yī)學(xué);2013年29期

10 張芹;張擁波;李繼梅;;腦出血研究進(jìn)展[J];神經(jīng)損傷與功能重建;2013年06期

相關(guān)會(huì)議論文 前4條

1 徐東菁;丁婷婷;孫皎;;羥基磷灰石納米顆粒誘導(dǎo)巨噬細(xì)胞凋亡及其與 HSP70相互關(guān)系的研究[A];2007年上海市醫(yī)用生物材料研討會(huì)論文匯編[C];2007年

2 寧萌;;淺議腹膜透析并發(fā)癥的產(chǎn)生原因及護(hù)理[A];2012年河南省腹膜透析護(hù)理新進(jìn)展培訓(xùn)班論文集[C];2012年

3 Gang Li;Rui-Ming Fan;Jia-Lin Chen;Chang-Ming Wang;You-Chao Zeng;Chong Han;Song Jiao;Xiang-Ping Xia;Wei Chen;Sheng-Tao Yao;;Neuroprotective effects of Argatroban and C5a receptor antagonist(PMX53)following intracerebral hemorrhage[A];2013年貴州省神經(jīng)外科年會(huì)論文集[C];2013年

4 趙俊;;TLR4在老年高血壓腦出血患者血腫周圍腦組織中的表達(dá)及意義[A];全國(guó)高血壓防治知識(shí)推廣培訓(xùn)班暨健康血壓中國(guó)行海南�？跁�(huì)論文綜合刊[C];2014年

相關(guān)博士學(xué)位論文 前10條

1 袁天明;宮內(nèi)感染/炎癥后未成熟腦星形細(xì)胞膠質(zhì)化的作用及機(jī)制研究[D];浙江大學(xué);2011年

2 羅春霞;腺苷A3受體激活在大鼠實(shí)驗(yàn)性蛛網(wǎng)膜下腔出血后早期腦損傷中的作用及機(jī)制研究[D];第三軍醫(yī)大學(xué);2011年

3 馮凱;18個(gè)重要炎癥相關(guān)基因SNP分析及TLR4基因5’區(qū)SNP功能研究[D];第三軍醫(yī)大學(xué);2004年

4 羅聰;超順磁性殼聚糖質(zhì)粒（pDsVEGF_（165）Red1-N1）明膠控釋微球促進(jìn)人工骨血管化的初步研究[D];重慶醫(yī)科大學(xué);2006年

5 廖文斌;人臍帶間充質(zhì)干細(xì)胞移植治療腦血管疾病的實(shí)驗(yàn)研究[D];中國(guó)協(xié)和醫(yī)科大學(xué);2009年

6 潘韞丹;核因子-κB對(duì)神經(jīng)病理性疼痛及其脊髓免疫炎癥因子表達(dá)的調(diào)節(jié)[D];中南大學(xué);2009年

7 薛云;CD14和TLR2基因多態(tài)性與中國(guó)漢族人群結(jié)核病易感性的關(guān)聯(lián)研究[D];浙江大學(xué);2010年

8 董良;P2X4受體在慢性嗎啡耐受中的作用機(jī)制[D];中南大學(xué);2010年

9 程瑩瑩;蛋白酶激活受體-1在凝血酶引起腦損傷中的作用[D];吉林大學(xué);2012年

10 劉寶華;CD163/HO-1信號(hào)通路與人腦出血后血腫周圍組織炎癥反應(yīng)的相關(guān)性[D];吉林大學(xué);2012年

相關(guān)碩士學(xué)位論文 前10條

1 王麗卿;丙泊酚減輕腦出血大鼠早期腦水腫和抑制其小膠質(zhì)細(xì)胞激活[D];浙江大學(xué);2011年

2 宋伶俐;人CD36抗原缺失的基因檢測(cè)及臨床意義[D];吉林大學(xué);2011年

3 趙玉林;上海地區(qū)獻(xiàn)血者IgA缺乏調(diào)查及CD36缺失表型的初步研究[D];華東師范大學(xué);2011年

4 胡坤;鼠小膠質(zhì)細(xì)胞TLR9的表達(dá)及其介導(dǎo)的抗HCV免疫機(jī)制的初步研究[D];寧夏醫(yī)科大學(xué);2011年

5 甘霖;TIMP-3質(zhì)粒轉(zhuǎn)染防止慢性排斥中血管病變的實(shí)驗(yàn)研究[D];重慶醫(yī)科大學(xué);2005年

6 韓麗芳;中國(guó)人群MEFV基因突變及其在炎癥反應(yīng)中的作用[D];暨南大學(xué);2006年

7 尹榕;Humanin和S14G-HN對(duì)β-淀粉樣蛋白和腦出血所致炎癥反應(yīng)的神經(jīng)保護(hù)作用[D];第四軍醫(yī)大學(xué);2007年

8 胡澤華;胰島素對(duì)內(nèi)毒素血癥幼鼠肝損傷保護(hù)作用的實(shí)驗(yàn)研究[D];廣西醫(yī)科大學(xué);2009年

9 馬麗霞;DOCK2對(duì)中性粒細(xì)胞凋亡和表達(dá)TLR4的影響[D];瀘州醫(yī)學(xué)院;2010年

10 于萍;多發(fā)性硬化的免疫機(jī)制[D];河北醫(yī)科大學(xué);2010年

本文編號(hào)：1802056