本文選題：多器官功能障礙綜合征 + 急性呼吸窘迫綜合征��； 參考：《第三軍醫(yī)大學(xué)》2005年博士論文

【摘要】：老年多器官功能障礙綜合征(MODSE)往往繼發(fā)于肺部感染且以肺損傷出現(xiàn)最早,表明老年肺臟更易受到脂多糖(LPS)的攻擊,在MODSE發(fā)生過(guò)程中起著更為關(guān)鍵的作用。其原因可能是老年肺臟對(duì)LPS敏感性增強(qiáng)所致。本課題采用油酸(OA)和LPS致傷SD大鼠,建立二次致傷MODSE和青年多器官功能障礙綜合征(MODSY)動(dòng)物模型對(duì)比觀察各自臟器損傷的特點(diǎn)及差異,在此模型的基礎(chǔ)上,檢測(cè)肺、心、肝、腎不同臟器組織中細(xì)胞因子TNF-α、IL-6蛋白及mRNA表達(dá),內(nèi)毒素含量,以及CD14、TLR4受體mRNA及蛋白表達(dá)變化,并檢測(cè)肺組織中轉(zhuǎn)錄因子NF-κB活化情況,從老年鼠肺組織CD14、TLR4受體易感性及其對(duì)內(nèi)毒素親和性的角度,探討老年肺易損機(jī)制,及其在MODSE發(fā)生中的作用。 方法: 1.建立OA/LPS二次致傷MODSE和MODSY大鼠模型。 2.ELISA法檢測(cè)血漿及肺、心、肝、腎組織中細(xì)胞因子TNF-α、IL-6蛋白含量,RT-PCR檢測(cè)上述組織中mRNA表達(dá)。 3.鱟試劑凝膠法檢測(cè)肺、心、肝、腎組織中內(nèi)毒素含量。 4.RT-PCR檢測(cè)肺、心、肝、腎組織中CD14、TLR4 mRNA表達(dá)水平,免疫組化方法檢測(cè)其蛋白表達(dá)。 5.免疫組化方法檢測(cè)肺組織中轉(zhuǎn)錄因子NF-κB活化情況。 結(jié)果: 1.OA/LPS致傷后2h,青年組和老年組PaO_2降至最低值(分別為67.5±8.66mmHg,59.3±7.41mmHg,P0.01),心、肝、腎生化指標(biāo)于6h達(dá)峰值(P0.05～0.01),且老年組臟器損害較同時(shí)相點(diǎn)青年組嚴(yán)重(P0.05～0.01)。符合動(dòng)物MODS診斷標(biāo)準(zhǔn)。 2.傷后2h,血清及肺、心、肝和腎組織中TNF-α、IL-6含量和組織中mRNA表達(dá)顯著升高達(dá)峰值,且持續(xù)高于正常對(duì)照組(P0.05～0.01),以肺組織升高幅度最大。老年組2h、6h時(shí)相點(diǎn)TNF-α、IL-6含量和mRNA表達(dá)均顯著高于同時(shí)相點(diǎn)的青年組(P0.05)。
[Abstract]:Multiple organ dysfunction syndrome (MODSE) in the elderly is usually secondary to pulmonary infection and the earliest occurrence of lung injury, indicating that the elderly lung is more vulnerable to the LPSs attack, and plays a more critical role in the pathogenesis of MODSE. This may be due to the increased sensitivity of the elderly lung to LPS. In this study, SD rats were injured by oleic acid (OAA) and lipopolysaccharide (LPS). The animal models of secondary injury MODSE and young multiple organ dysfunction syndrome (MODSYS) were established to observe the characteristics and differences of organ injury. On the basis of the model, lung, heart and liver were detected. The expression of TNF- 偽 and IL-6 protein and mRNA, the content of endotoxin, the expression of CD14 TLR4 receptor mRNA and protein in different organs of kidney, and the activation of transcription factor NF- 魏 B in lung tissue were detected. From the point of view of susceptibility of CD14 TLR4 receptor and its affinity to endotoxin in aged rats, the mechanism of lung damage and its role in the pathogenesis of MODSE were discussed. Methods: 1. The model of MODSE and MODSY rats with secondary injury induced by OAP / LPS was established. 2. Elisa was used to detect plasma, lung, heart and liver. The protein content of TNF- 偽 and IL-6 in renal tissue was detected by RT-PCR. 3. 3. The content of endotoxin in lung, heart, liver and kidney was detected by Limulus amebocyte lysate gel method. 4. The expression of CD14 TLR4 mRNA in lung, heart, liver and kidney was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect its protein expression. 5. 5. The activation of NF-魏 B in lung tissue was detected by immunohistochemistry. Results: 1. At 2 h after OAP / LPS injury, PaO-2 decreased to the lowest value in young group and old group (67.5 鹵8.66 mm HgGN 59.3 鹵7.41 mm HgP 0.01, heart, liver, respectively). The renal biochemical index reached the peak value at 6 h, and the organ damage in the elderly group was more serious than that in the young group at the same time. In accordance with animal mods diagnostic criteria. 2. TNF- 偽 IL-6 content and mRNA expression in serum, lung, heart, liver and kidney increased to the peak at 2 h after injury, and continued to be higher than that in the normal control group (P 0.05), especially in lung tissue. The content and mRNA expression of TNF- 偽 IL-6 in the aged group were significantly higher than those in the young group at 2 h or 6 h.
【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】：2005
【分類號(hào)】：R363

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本文編號(hào)：2045182