本文選題：胰腺　切入點(diǎn)：缺血再灌注　出處：《中國醫(yī)科大學(xué)》2010年博士論文

【摘要】： 前言 在休克、胰腺手術(shù)、胰腺移植中,胰腺的缺血再灌注(I／R)損傷仍然是一個重要的臨床問題。損傷的主要機(jī)制是產(chǎn)生大量氧自由基和缺血性炎癥。許多研究表明,胰腺的I／R能增加血中白細(xì)胞數(shù),氧自由基的生產(chǎn),及細(xì)胞因子的釋放,從而引起急性胰腺炎及全身炎癥反應(yīng)綜合癥。 在全身炎癥反應(yīng)綜合征中肺臟是首位受累的靶器官。因為,肺臟是唯一接受全部心臟排出量的器官,受循環(huán)中炎性細(xì)胞及介質(zhì)的損傷最大,隔離在肺部的活化炎性細(xì)胞和炎性胰腺釋放的蛋白酶都會誘發(fā)急性肺損傷。急性胰腺炎是胰酶在胰腺內(nèi)被激活后引起胰腺組織自身消化的一種炎癥反應(yīng)性疾病,主要表現(xiàn)為血清淀粉酶和脂肪酶升高。急性胰腺炎相關(guān)性肺損傷(acute pancreatitis-associated lung injury, APALI)發(fā)病機(jī)制復(fù)雜,可通過某種機(jī)制導(dǎo)致胰腺酶的不適當(dāng)激活,這種機(jī)制包括酶解作用衍生的催化劑激活炎性細(xì)胞,白細(xì)胞的釋放,及氧化和亞硝化應(yīng)激的發(fā)生,從而改變氣道反應(yīng)性。 目前研究認(rèn)為核因子κB(nuclear factor-KB)在其中扮演重要角色,其活化被認(rèn)為是急性胰腺炎重要的早期事件。(NF-κB)是一種轉(zhuǎn)錄調(diào)節(jié)因子,在細(xì)胞因子介導(dǎo)的感染、炎癥反應(yīng)、氧化應(yīng)激、細(xì)胞增生、細(xì)胞凋亡等過程中起重要作用。正常生理情況下,NF-κB以無活性的形式存在于多種細(xì)胞的胞質(zhì)中,激活后促進(jìn)多種細(xì)胞因子的基因轉(zhuǎn)錄,在炎癥反應(yīng)復(fù)雜的細(xì)胞因子網(wǎng)絡(luò)中,NF-κB的活化可能是一個中心環(huán)節(jié),研究表明NF-κB通過促進(jìn)TNF-α、IL-6、IL-8、細(xì)胞間黏附分子(Intercellular adhesion molecular, ICAM)等基因的轉(zhuǎn)錄而參與肺損傷的發(fā)生,其中ICAM-1在胰腺炎引起的肺損傷中最受關(guān)注。ICAM-1屬于免疫球蛋白超家族成員,其在人體內(nèi)的分布十分廣泛,炎癥介質(zhì)能明顯上調(diào)血管內(nèi)皮細(xì)胞和其它非造血細(xì)胞ICAM-1的表達(dá)。肺血管內(nèi)皮上表達(dá)的ICAM-1結(jié)合活化的白細(xì)胞表面的整合素CDllb／8β是白細(xì)胞的黏附、游走、聚集過程中的關(guān)鍵環(huán)節(jié),其過度表達(dá)可以促進(jìn)局部炎性反應(yīng)發(fā)生。 巨噬細(xì)胞的作用越來越引起人們的重視。近年研究表明巨噬細(xì)胞活化可能是急性胰腺炎時發(fā)生肺損傷的的重要途徑之一�；罨木奘杉�(xì)胞可以釋放許多生物活性物質(zhì),如細(xì)胞因子、花生四烯酸等,均為前炎性反應(yīng)介質(zhì),可以介導(dǎo)PMN等釋放多種炎癥反應(yīng)介質(zhì)。巨噬細(xì)胞移動抑制因子(macro-phage migration inhibitory facter, MIF)具有抑制巨噬細(xì)胞游走,促進(jìn)巨噬細(xì)胞的黏附和在炎癥局部浸潤的作用,并可刺激炎癥細(xì)胞分泌TNF、IL-1等促炎性細(xì)胞因子。巨噬細(xì)胞炎癥蛋-2(macrophage inflammatory protein 2, MIP-2)是大鼠ELR+(含谷-亮-精氨酸功能基序)CXC類趨化性細(xì)胞因子,在功能上和人類IL-8同源,是中性粒細(xì)胞的主要趨化細(xì)胞因子。本研究通過大鼠胰腺缺血再灌注模型,探討大鼠胰腺缺血再灌注時,合并肺損傷、誘導(dǎo)氣道高反應(yīng)性中的作用；并探討NF-κB與ICAM-1mRNA表達(dá)及MIF與MIP-2在胰腺缺血再灌注并發(fā)肺損傷中的作用。 材料與方法 一、動物模型和樣品制備 1、I／R動物模型 通過阻斷胃十二指腸動脈和脾動脈2小時,再灌注6小時誘導(dǎo)胰腺缺血。假手術(shù)組以相同的手術(shù)方法切開顯露胃十二指腸動脈和脾動脈,但不夾閉血管。 2、試驗取材 取右股靜脈血作為血樣。實(shí)驗結(jié)束時向肺內(nèi)注入5ml生理鹽水,獲取肺灌洗液。Sham組沒有阻斷動脈,其值作為未阻斷的基礎(chǔ)對照值。切取肺組織,-80℃冷凍保存。 二、觀察指標(biāo)及測定方法 1、胰腺缺血再灌注誘導(dǎo)的氣道高反應(yīng)性研究 (1)收集血液樣本離心后,使用Kodak Ektachem DT60分析器(羅切斯特,紐約)測量血漿中分離的淀粉酶含量,以IU／L表示。 (2)高效液相色譜法測量血液中源自一氧化氮(NO)的亞硝酸鹽和硝酸鹽陰離子 (3)通過分光熒光計測量血液中甲基胍。 (4)白細(xì)胞計數(shù)測量肺灌洗液標(biāo)本中的WBC。 (5)通過酶聯(lián)免疫測定血液中腫瘤壞死因子(TNF-α)的表達(dá)量。按試劑盒說明書進(jìn)行操作。顯色后用酶標(biāo)儀(波長450nm)比色讀數(shù),根據(jù)標(biāo)準(zhǔn)曲線求出TNF-α數(shù)值。 (6)全身體積描記法(Buxco co)測定氣道對乙酰甲膽堿的反應(yīng)變化。雙室體描儀由頭室和體室組成,各置一流量傳感器,分別用于測量鼻部呼吸引起的氣流變化和胸廓運(yùn)動引起的氣流變化。流量傳感器感受到的流量變化轉(zhuǎn)變成電信號,經(jīng)放大器放大,轉(zhuǎn)換成數(shù)字信號后,通過軟件(BioSystem XA software with NAM analyzer)分析,計算出大鼠氣道基線增強(qiáng)暫停系數(shù)(the baseline enhanced pause, Penh)。 (7)實(shí)時監(jiān)測PCR采用mRNA分離試劑盒分離肺組織中的mRNA;使用ABI公司7000型檢測棱鏡(應(yīng)用生物系統(tǒng)公司)實(shí)時監(jiān)測PCR擴(kuò)增反應(yīng)。通過實(shí)時聚合酶鏈反應(yīng)測定肺組織中的iNOS的mRNA表達(dá)和腫瘤壞死因子(TNF-α)的表達(dá)。 2、NF-κB與ICAM-1在I／R并發(fā)肺損傷的作用研究 (1)組織病理學(xué)評分：取各組大鼠胰頭部組織和右肺下葉組織經(jīng)4%多聚甲醛固定、石蠟包埋、HE染色,光鏡觀察組織病理學(xué)變化并進(jìn)行評分。 (2)收集血液樣本離心后,使用Kodak Ektachem DT60分析器(羅切斯特,紐約)測量血漿中分離的淀粉酶含量,以IU／L表示。 (3)肺組織MPO檢測按照試劑盒說明書操作。將肺組織機(jī)械勻漿后水浴、比色、參照如下公式計算：MPO(U／g)濕片=(測定管OD值-對照組OD值)／11.3×取樣量(g) (4) Western Blot法檢測肺組織ICAM-1蛋白表達(dá),凝膠成像系統(tǒng)對結(jié)果照相及測定條帶的面積和灰度值,以目的條帶的面積×灰度值/Actin條帶的面積×灰度值的比值代表蛋白的表達(dá)水平。 (5)NF-κB相對活性檢測：結(jié)果用Leica Q500Mc圖像分析系統(tǒng)進(jìn)行密度分析,以灰度值表示NF-κB相對活性變化。 3、I／R并發(fā)肺損傷中MIF與MIP-2的表達(dá)及意義研究 (1)組織病理學(xué)評分：取各組大鼠胰頭部組織和右肺下葉組織經(jīng)4%多聚甲醛固定、石蠟包埋、HE染色,光鏡觀察組織病理學(xué)變化并進(jìn)行評分。 (2)收集血液樣本離心后,使用Kodak Ektachem DT60分析器(羅切斯特,紐約)測量血漿中分離的淀粉酶含量,以IU／L表示。 (3)肺組織MPO檢測按照試劑盒說明書操作。將肺組織機(jī)械勻漿后水浴、比色、參照如下公式計算：MPO(U／g)濕片=(測定管OD值-對照組OD值)／11.3×取樣量(g) (4)RT-PCR法檢測肺組織MIF mRNA的表達(dá),采用Trizol一步法提取肺組織總RNA,紫外分光光度儀測定RNA濃度。用TC 21000數(shù)據(jù)圖像分析系統(tǒng)分析各條帶灰度值,得MIF/GADPH的灰度比值,即為MIF mRNA的相對表達(dá)值。 (5)肺組織MIP-2含量測定：肺組織用10倍體積的預(yù)冷勻漿介質(zhì)制成勻漿,一份用ELISA法檢測MIP-2濃度,采用ELISA全自動檢測儀按rMIP-2/GRO-βELISA試劑盒供應(yīng)商提供的說明書設(shè)定反應(yīng)步驟；一份用全自動生化分析儀測定蛋白含量。 4、統(tǒng)計學(xué)分析 采用SPSS 13.0軟件進(jìn)行統(tǒng)計學(xué)分析。對數(shù)據(jù)進(jìn)行正態(tài)性檢驗后,用均數(shù)(Mean)和標(biāo)準(zhǔn)差(SD)描述正態(tài)分布數(shù)據(jù)的集中趨勢和離散水平。組間各檢測指標(biāo)比較采用t檢驗,試驗前后比較采用配對t檢驗,p值0.05認(rèn)為有統(tǒng)計學(xué)意義。 結(jié)果 1、胰腺缺血再灌注誘導(dǎo)的氣道高反應(yīng)性研究 本實(shí)驗研究發(fā)現(xiàn)I／R組小鼠血中的一氧化氮,羥自由基,淀粉酶,腫瘤壞死因子,白細(xì)胞濃度的顯著升高。在缺血再灌注(I／R)后肺組織中iNOS和腫瘤壞死因子的mRNA的表達(dá)明顯增加,肺功能的數(shù)據(jù)顯示,胰腺的缺血／再灌注(I／R)誘導(dǎo)氣道對乙酰甲膽堿的反應(yīng)大量增加；與假手術(shù)組相比,I／R組中的PenH顯著增加,而且灌洗液白細(xì)胞明顯增加。 2、NF-κB與ICAM-1在I／R并發(fā)肺損傷的作用研究 I／R組大鼠胰腺和肺組織病理學(xué)評分分別為5.94±0.72和6.42±0.65；顯著的高于Sham組大鼠病理評分(分別為：0.20±0.14和0.27±0.31)(p0.05)；Sham組大鼠血清中淀粉酶的水平為1198.4±121.7；I／R組大鼠血清中淀粉酶的水平為3719.6±523.8；兩組間差異達(dá)到統(tǒng)計學(xué)意義(p0.05)。與Sham組大鼠比較,胰腺缺血再灌注可顯著的增高肺組織中MPO水平的表達(dá)(0.74±0.06)(p0.05)；Sham組大鼠肺組織中ICAM-1蛋白和ICAM-1 mRNA微弱表達(dá),I／R組大鼠肺組織中ICAM-1蛋白和ICAM-1 mRNA表達(dá)增高,其表達(dá)水平分別為0.47±0.03和1.12±0.07；胰腺缺血再灌注后可使大鼠肺組織中NF-κB活性水平顯著的增高。 3、I／R并發(fā)肺損傷中MIF與MIP-2的表達(dá)及意義研究 Sham組胰腺組織和肺組織病理評分分別為2.14±0.06和0.37±0.14；I／R組胰腺組織和肺組織病理評分分別為8.52±1.17和4.71±0.30；兩組間病理評分差異達(dá)到統(tǒng)計學(xué)意義(p0.05)。胰腺缺血再灌注可顯著的增高血清中淀粉酶和肺組織中MPO水平的表達(dá)。sham組大鼠血清中MIF和肺組織中MIFmRNA表達(dá)微弱,,而I／R組大鼠血清中MIF和肺組織中MIFmRNA表達(dá)增高。Sham組大鼠肺組織中MIP-2活性水平為23.9±5.8；胰腺缺血再灌注后可使大鼠肺組織中MIP-2活性水平顯著的增高(91.5±12.1)。 結(jié)論 1、胰腺I／R誘導(dǎo)全身炎癥反應(yīng)及肺內(nèi)白細(xì)胞(WBC)的增加。再灌注組中氣道的高反應(yīng)性可能是因為氣道炎癥,后者增加肺內(nèi)WBC的聚集及肺組織中iNOS的表達(dá)、腫瘤壞死因子、炎癥介質(zhì)的表達(dá)。 2、胰腺缺血再灌注損傷可增高肺組織ICAM-1蛋白和ICAM-1基因水平表達(dá)。胰腺缺血2小時再灌注6小時后肺組織NF-κB水平增高。 3、胰腺缺血再灌注損傷可增高血清和肺組織MIF和MIFmRNA基因水平表達(dá)。肺組織MIP-2含量增高,作為早期的促炎性細(xì)胞因子,MIP-2介導(dǎo)了肺損傷。
[Abstract]:Preface
In shock, pancreatic surgery, transplantation of pancreas, pancreatic ischemia reperfusion injury (I / R) is still a major clinical problem. The main mechanism of injury is to generate a large number of oxygen free radicals and ischemic inflammation. Many studies show that pancreatic I / R can increase the number of white blood cells in the blood, oxygen free radical the production and release of cytokines, which cause acute pancreatitis and systemic inflammatory response syndrome.
In systemic inflammatory response syndrome in the lung is the target organ involvement. First because the lung is only acceptable for all cardiac output organs, by circulating inflammatory cells in the medium and the maximum damage isolation will induce acute lung injury in the activation of inflammatory cells and pancreatic proteases released from the lungs. Acute pancreatitis is a kind of inflammatory disease in the pancreas trypsin activated pancreatic tissue by their own digestion, mainly for serum amylase and serum lipase. Acute pancreatitis associated lung injury (acute pancreatitis-associated lung injury, APALI) complex pathogenesis, inappropriate activation of pancreatic enzymes can be caused by some mechanism, this mechanism comprises a catalyst derived enzymatic activation of inflammatory cells, white blood cells release and oxidative and nitrosative stress, thus changing the airway reactivity.
The present study of nuclear factor kappa B (nuclear factor-KB) which plays an important role in the activation, is considered to be an important early event in acute pancreatitis. (NF- B) is a transcription factor, cytokine mediated infection, inflammation, oxidative stress, cell proliferation, plays an important role in the process of cell apoptosis. Under normal physiological conditions, cytoplasmic NF- kappa B exists in the form of activity in a variety of cells, cytokines promote gene transcription after activation, in the network of inflammatory cytokines in complex NF- kappa B activation may be a key link, studies show that NF- kappa B through promotion of TNF- alpha, IL-6, IL-8, intercellular adhesion molecule (Intercellular adhesion, molecular, ICAM) gene transcription in lung injury, lung injury in the ICAM-1 pancreatitis caused by the most popular.ICAM-1 belongs to the immunoglobulin super family Family members, it is widely distributed in the human body, inflammatory mediators could significantly up regulate the expression of vascular endothelial cells and other non hematopoietic cells. The expression of ICAM-1 in pulmonary vascular endothelial ICAM-1 on the surface of activated white blood cells with CDllb / beta 8 integrin adhesion, leukocyte migration, aggregation of key links in the process of the overexpression can promote the occurrence of local inflammatory reaction.
More and more people pay attention to macrophages. Recent studies suggest that macrophage activation may be an important pathway of lung injury in acute pancreatitis. Activated macrophages can release many bioactive substances, such as cytokines, four arachidonic acid, are proinflammatory mediators, can mediate PMN release various inflammatory reaction medium. Macrophage migration inhibitory factor (macro-phage migration inhibitory facter, MIF) can inhibit macrophage migration, promote macrophage adhesion and infiltration in inflammation, and inflammatory cells can stimulate the secretion of TNF, IL-1 and proinflammatory cytokines. Inflammatory macrophages (macrophage inflammatory egg -2 protein 2, MIP-2 (ELR+) rat Hangu bright arginine motifs) CXC chemotactic cytokines, in function and human IL-8 is homologous, neutrophil The main chemotactic cytokines. The ischemia reperfusion model of ischemia reperfusion, with lung injury, induced airway hyperresponsiveness in action; and to explore the role of NF- K B and the expression of ICAM-1mRNA and MIF and MIP-2 in pancreatic ischemia reperfusion pulmonary injury.
Materials and methods
An animal model, and sample preparation
1, I / R animal model
By blocking the gastroduodenal artery and the splenic artery for 2 hours and 6 hours of reperfusion induced pancreatic ischemia. Sham operation group with the same surgical incision and exposure of the gastroduodenal artery and the splenic artery, but without occlusion of blood vessels.
2, test materials
Take the right femoral vein as the blood samples. 5ml saline was injected into the lungs to the end of the experiment, obtain the lung lavage fluid.Sham group without artery occlusion, its value as a basis for not blocking the control value. Cut the lung tissue, freezing storage at -80.
Two, observation index and determination method
1, study on airway hyperresponsiveness induced by ischemia reperfusion of pancreas
(1) blood samples were collected after centrifugation, using Kodak Ektachem DT60 analyzer (Rochester, New York) amylase content in plasma separation and measurement, using IU / L.
(2) HPLC measurement of blood from nitric oxide (NO) nitrite and nitrate anions
(3) by spectrofluorometer. Measurement of blood in methyl guanidine
(4) white blood cell count measurement of lung lavage fluid specimens in WBC.
(5) determination of blood tumor necrosis factor by ELISA (TNF- alpha) expression. According to the operation instructions Kit. After coloration with a microplate reader (wavelength 450nm) colorimetric readings, TNF- alpha numerical calculated according to the standard curve.
(6) whole-body plethysmography (Buxco CO) determination of airway reactivity to methacholine changes. Using double chamber plethysmography chamber and head body chambers, each provided with a flow sensor for measuring changes in nasal airflow were caused by respiratory airflow changes and thoracic movement caused by changes in the flow sensor flow change. Is feeling into electrical signals, amplified by the amplifier, after converted into digital signal by software (BioSystem XA software with NAM analyzer) analysis, calculate the baseline airway increased in rats (the baseline enhanced pause suspended coefficient, Penh).
(7) real-time monitoring of PCR using mRNA Isolation Kit from the lung tissue of mRNA; using ABI type 7000 prism detection (application Bio System Inc) amplification for real-time monitoring of PCR. The expression of mRNA and tumor necrosis factor iNOS in lung tissue were measured by real-time polymerase chain reaction (TNF- alpha) expression.
2, NF- kappa B and role of ICAM-1 in I / R complicated with lung injury
(1) histopathological scores of rats in each group: take the head of the pancreas tissue and the lower lobe of the right lung tissue was fixed by 4% paraformaldehyde, embedded in paraffin, HE staining to observe the pathological changes and evaluated by light microscope.
(2) blood samples were collected after centrifugation, using Kodak Ektachem DT60 analyzer (Rochester, New York) amylase content in plasma separation and measurement, using IU / L.
(3) the detection of MPO in lung tissue according to the kit instructions. The lung tissue homogenate after mechanical water bath, colorimetric, refer to the following formula: MPO (U / g) = (wet tube OD value of control group / OD) 11.3 x sample volume (g)
(4) to detect the expression of ICAM-1 protein in lung tissue of Western Blot method, gel imaging system on the photographic and determination of strip size and gray value, to strip the area * gray value expression represented by area /Actin band gray value X protein.
(5) to detect the relative activity of NF- K B: the density analysis using Leica Q500Mc image analysis system to the gray value of NF- kappa B relative activity changes.
3, to study the expression and significance of I / R MIF and MIP-2 in acute lung injury
(1) histopathological scores of rats in each group: take the head of the pancreas tissue and the lower lobe of the right lung tissue was fixed by 4% paraformaldehyde, embedded in paraffin, HE staining to observe the pathological changes and evaluated by light microscope.
(2) blood samples were collected after centrifugation, using Kodak Ektachem DT60 analyzer (Rochester, New York) amylase content in plasma separation and measurement, using IU / L.
(3) the detection of MPO in lung tissue according to the kit instructions. The lung tissue homogenate after mechanical water bath, colorimetric, refer to the following formula: MPO (U / g) = (wet tube OD value of control group / OD) 11.3 x sample volume (g)
(4) to detect the expression of MIF mRNA in lung tissue by RT-PCR, total RNA was extracted from lung tissue using Trizol method, RNA concentration was determined by UV spectrophotometer. The system analysis with the gray value of TC 21000 data to image analysis, gray level ratio MIF/GADPH, the relative expression of MIF mRNA values.
(5) to determine the content of MIP-2 in lung tissue: the lung tissue was homogenized with pre cooling medium 10 times the volume of the homogenate, a ELISA method was used to detect the concentration of MIP-2, according to the rMIP-2/GRO- beta ELISA kit provided by ELISA automatic tester instructions set a reaction step; by using automatic biochemical analyzer for the determination of protein content in animals.
4, statistical analysis
Statistical analysis was performed using SPSS 13 software. The test of normality of data, with the mean (Mean) and standard deviation (SD) described a normal distribution of data and discrete levels. All indexes between groups were compared by t test before and after the test, compared with paired t test, P value of 0.05 that have statistical significance.
Result
1, study on airway hyperresponsiveness induced by ischemia reperfusion of pancreas
This study found that nitric oxide in I / R mice blood, hydroxyl radical, amylase, tumor necrosis factor, significantly increased leukocyte concentration. In ischemia / reperfusion (I / R) expression of iNOS and tumor necrosis factor after mRNA in the pulmonary tissue increased significantly, lung function data show that the pancreas the ischemia / reperfusion (I / R) induced airway reactivity to methacholine increased; compared with sham operation group, I / R in the PenH group increased significantly, and lavage leucocyte increased significantly.
2, NF- kappa B and role of ICAM-1 in I / R complicated with lung injury
The pathological group of rat pancreas and lung tissue I / R scores were 5.94 + 0.72 and 6.42 + 0.65; significantly higher than the group Sham rats pathological score (respectively: 0.20 + 0.14 and 0.27 + 0.31) (P0.05); serum amylase levels in rats of Sham group is 1198.4 + 121.7 / I; the rats in group R serum amylase level was 3719.6 + 523.8; the difference between the two groups reached statistical significance (P0.05). Compared with Sham rats, the expression level of MPO increased significantly in the lung tissues of pancreatic ischemia-reperfusion (0.74 + 0.06) (P0.05); ICAM-1 protein and ICAM-1 mRNA weak expression the lung tissue in Sham rats, increased ICAM-1 protein and ICAM-1 mRNA expression in lung tissue of rats in group I / R, the expression levels were 0.47 + 0.03 and 1.12 + 0.07; pancreatic ischemia reperfusion injury can make NF- kappa B activity in lung tissue of rats increased significantly.
3, to study the expression and significance of I / R MIF and MIP-2 in acute lung injury
Pancreas and lung tissue in Sham group pathological score were 2.14 + 0.06 and 0.37 + 0.14; pathology of lung and pancreatic tissues of I / R scores were 8.52 + 1.17 and 4.71 + 0.30; difference between the pathological scores of the two groups reached statistical significance (P0.05). The serum expression of.Sham in pancreatic ischemia reperfusion rats the level of MPO increased significantly in serum amylase and lung tissue in MIF and lung tissue MIFmRNA expression was weak, while MIF, lung tissue and serum I / R rats the expression of MIFmRNA in.Sham group increased the level of MIP-2 activity in the lung tissues of rats was 23.9 + 5.8; pancreatic ischemia reperfusion injury can make the levels of MIP-2 activity in lung tissue of rats was significantly increased (91.5 + 12.1).
conclusion
In 1, pancreatic I / R induced systemic inflammatory response and lung leukocyte (WBC) increased. Then airway hyperresponsiveness in reperfusion group may be due to airway inflammation, which increases the expression of iNOS in lung tissue and lung gathered in WBC, tumor necrosis factor, expression of inflammatory mediators.
2, can increase ICAM-1 protein and ICAM-1 expression in lung ischemia reperfusion injury of pancreas. The level of NF- K B in lung tissue of pancreatic ischemia reperfusion for 2 hours after 6 hours.
3, can increase the MIF and MIFmRNA gene expression levels in serum and lung tissue of pancreatic ischemia reperfusion injury. The increased content of MIP-2 in lung tissue, as a pro-inflammatory cytokine early, MIP-2 mediated lung injury.

【學(xué)位授予單位】：中國醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2010
【分類號】：R363

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 楊秀紅,張連元,孫樹勛,董淑云,門秀麗,景有伶,張一兵;一氧化氮在大鼠肢體缺血再灌注后肺損傷中的作用[J];生理學(xué)報;2002年03期

2 張喜平;吳承鈞;李志軍;;重癥急性胰腺炎并發(fā)肺損傷的研究進(jìn)展[J];世界華人消化雜志;2008年03期

3 張喜平;陸貝;;核因子-κB在重癥急性胰腺炎發(fā)病過程及MODS中的作用[J];醫(yī)學(xué)研究雜志;2006年11期

4 盧彥珍,董傳仁,張友云,鄭漢巧,涂淑珍,歐陽靜萍;非創(chuàng)傷缺血預(yù)處理對大鼠缺血再灌注心肌的作用[J];中國病理生理雜志;1999年03期

5 中華醫(yī)學(xué)會呼吸病學(xué)分會,劉又寧;急性肺損傷/急性呼吸窘迫綜合征的診斷標(biāo)準(zhǔn)(草案)[J];中華結(jié)核和呼吸雜志;2000年04期

6 鄭曉春,陳彥青,黃風(fēng)怡,彭玲,于榮國,林麗珊,吳曉丹;抗壞血酸對腸缺血再灌注大鼠肺損傷的保護(hù)作用[J];中華麻醉學(xué)雜志;2005年08期

7 程石,何三光,張佳林;肺泡巨噬細(xì)胞活化在急性壞死性胰腺炎大鼠肺損傷中的作用[J];中華外科雜志;2002年08期

8 姜鵬,王建春,錢桂生;急性肺損傷大鼠肺組織PPARαmRNA表達(dá)的變化[J];中國誤診學(xué)雜志;2005年06期

9 Tamás Letoha;Csaba Somlai;Tamáas Takács;Annamária Szabolcs;Katalin Jármay;Zoltán Rakonczay Jr;Péter Hegyi;Ilona Varga;József Kaszaki;István Krizbai;Imre Boros;Ern(?) Duda;Erzsébet Kusz;Botond Penke;;A nuclear import inhibitory peptide ameliorates the severity of cholecystokinin-induced acute pancreatitis[J];World Journal of Gastroenterology;2005年07期

10 ;Effect of BN52021 on NFκ-Bp65 expression in pancreatic tissues of rats with severe acute pancreatitis[J];World Journal of Gastroenterology;2007年06期

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