本文選題：肺損傷　切入點：硫化氫　出處：《中國人民解放軍軍醫(yī)進修學(xué)院》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： 背景和目的： 肝臟移植術(shù)、肝臟大部切除術(shù)臨床上極為常見,術(shù)中造成全肝缺血再灌注損傷,勢必給其它遠隔臟器帶來損傷,肝缺血及門靜脈瘀血可產(chǎn)生大量有害介質(zhì),在肝血流恢復(fù)后經(jīng)由心臟立即傾注入肺,造成急性肺損傷,給移植成功帶來了巨大的困難,嚴(yán)重影響著術(shù)后病人的存活率。 本實驗通過手術(shù)方法建立大鼠全肝缺血再灌注模型,從術(shù)后肺臟結(jié)構(gòu)及功能改變,肺內(nèi)各類致傷因子的動態(tài)變化,以及鈣調(diào)神經(jīng)磷酸酶、硫化氫／胱硫醚-γ-裂解酶、水通道蛋白、線粒體能量代謝的改變等方面,較全面研究創(chuàng)傷后肺損傷的發(fā)病機制。并應(yīng)用硫氫化鈉、他克莫司、螺內(nèi)酯、甲潑尼龍進行干預(yù),進一步研究術(shù)后肺臟損傷的機制及藥物的作用途徑,以尋找有效的干預(yù)措施。 本實驗分為兩部分：一、全肝缺血再灌注致大鼠肺臟損傷機制及藥物干預(yù)對其影響；二、全肝缺血再灌注大鼠肺臟損傷的線粒體機制及其藥物干預(yù) 方法：通過手術(shù)方法建立大鼠全肝缺血再灌注的創(chuàng)傷模型。 第一部分：雄性Wistar大鼠184只,隨機分為23組,每組8只：正常對照組、缺血20min再灌注0h、2h、6h、12h、24h、48h、72h組、缺血40分鐘再灌注0h、6h、72h組；FK-506、MP、NaHS、Spiron空白對照組及20min+6h干預(yù)組;MP、Spiron 40min+6h及40min+72h干預(yù)組。第二部分：雄性Wistar大鼠80只,隨機分為10組,每組8只：正常對照組、缺血20min再灌注6h組、FK-506、MP、NaHS、Spiron空白對照組及20min+6h干預(yù)組。 動態(tài)檢測各組大鼠血漿硫化氫(H2S)、丙二醛(MDA)、血管緊張素II(AngⅡ)、醛固酮(ALD)、腫瘤壞死因子-a(TNF-a)、白介素-8(IL-8)的變化,檢測肺臟濕干重比值、CSE活性,細(xì)胞間粘附分子(ICAM-1)、核因子NF-κB、IL-8、AQP1含量,鈣調(diào)神經(jīng)磷酸酶(CaN)含量、活性及mRNA表達,測定線粒體呼吸功能、膜電位及粒體酶的變化,觀察光鏡及電鏡下肺組織形態(tài)結(jié)構(gòu)的變化。 結(jié)果： 第一部分：與正常對照組比較,缺血20min再灌注組,血清TNF-a、血清及肺臟IL-8、血漿MDA、血漿AngⅡ、血漿H2S、肺臟W/D、ICAM-1、NF-κB水平在缺血期即開始升高,再灌注后持續(xù)升高,于再灌注2-12h之間各達到峰值后降低；肺臟AQP1蛋白表達缺血再灌注后逐漸降低,于再灌注6h時降到最低值；肺臟CSE、血漿及肺臟ALD、肺臟CaN含量、活性及mRNA表達缺血再灌注后升高,分別于2h、6-12h出現(xiàn)兩次峰值后逐漸下降,多數(shù)監(jiān)測指標(biāo)于再灌注后72h恢復(fù)至接近正常值水平；光鏡及電鏡結(jié)果顯示缺血再灌注后6h肺臟組織損傷最為嚴(yán)重。缺血40min再灌注組表現(xiàn)相同的變化趨勢,大多數(shù)指標(biāo)變化程度較缺血20min相應(yīng)組更為顯著,肺組織損傷較缺血20min組更為嚴(yán)重；應(yīng)用FK506、Spiron、MP、NaHS藥物干預(yù)后,觀察到創(chuàng)傷最重時間點的肺組織各項指標(biāo)出現(xiàn)不同程度改善,提示藥物對肺組織損傷起到了不同程度的保護作用。第二部分：與正常對照組比較,缺血再灌注后,肺臟線粒體ATP酶活性改變,RCR、P/O、膜電位均降低,應(yīng)用FK506、Spiron、MP、NaHS藥物干預(yù)后,各項指標(biāo)均有不同程度的改善。 結(jié)論： 全肝缺血再灌注模型中,缺血和再灌注兩個階段均可造成肺臟損傷,且隨缺血時間延長,肺組織損傷加重,肺臟損傷以再灌注6h損傷最為嚴(yán)重。各種致傷因子作用于肺組織引起損傷,損傷過程中,鈣調(diào)神經(jīng)磷酸酶、內(nèi)源性H2S/CSE這兩條信號轉(zhuǎn)導(dǎo)通路的改變,水通道蛋白的減低,線粒體能量代謝障礙均參與了肺臟的損傷,是創(chuàng)傷致肺損傷的重要病理生理學(xué)基礎(chǔ)之一。應(yīng)用FK506、Spiron、MP、NaHS藥物干預(yù)后,藥物通過作用于上述機制對缺血再灌注所致肺損傷起到不同程度的保護作用。
[Abstract]:Background and purpose:
Liver transplantation, liver resection on clinical is extremely common, resulting in hepatic ischemia reperfusion injury, is bound to the other remote organ damage, liver ischemia and portal vein blood stasis can produce a lot of harmful medium in the liver after restoration of blood flow through the heart immediately poured into the lungs, causing acute lung injury, to transplant success has brought great difficulties, seriously affected the survival rate of patients after operation.
This experiment established through operation. The total hepatic ischemia-reperfusion in rats model, from the change of lung structure and function after operation, the dynamic changes of all kinds of lung injury factor, and calcineurin / H2S, cystathionine gamma lyase, water channel protein, mitochondrial energy metabolism changes, compared with a comprehensive study of the pathogenesis of lung injury after trauma. And the application of sodium hydrosulfide, tacrolimus, spironolactone, methylprednisolone intervention effect, further study and drug mechanism of lung injury after operation, in order to find out the effective intervention measures.
The experiment is divided into two parts: first, the mechanism of lung injury induced by total hepatic ischemia reperfusion and the effect of drug intervention; two, mitochondria mechanism and drug intervention of lung injury in rats after total hepatic ischemia-reperfusion.
Methods: the traumatic model of rat liver ischemia-reperfusion was established by operation.
The first part: 184 male Wistar rats were randomly divided into 23 groups, 8 rats in each group: normal control group, ischemia reperfusion 20min, 0h, 2h, 6h, 12h, 24h, 48h, 72h group, 40 min of ischemia reperfusion 0h, 6h, FK-506, MP, 72h; NaHS, Spiron control group and 20min+6h intervention group; MP, Spiron 40min+6h and 40min+72h group. The second part: 80 male Wistar rats were randomly divided into 10 groups, 8 rats in each group: normal control group, ischemia reperfusion group, 20min 6h, FK-506, MP, NaHS, Spiron control group and 20min+6h group.
Rat plasma hydrogen sulfide (H2S), dynamic detect malondialdehyde (MDA), angiotensin II (Ang II), aldosterone (ALD), tumor necrosis factor -a (TNF-a), interleukin -8 (IL-8) change detection, lung wet to dry weight ratio, CSE activity, cell adhesion molecule (ICAM-1) nuclear factor kappa B, NF-, IL-8, AQP1 content, calcineurin (CaN) content, activity and expression of mRNA, mitochondrial respiratory function, changes of membrane potential and mitochondrial enzyme, observe the morphological changes in lung tissue under the light microscope and electron microscope.
Result錛，

本文編號：1636864