本文選題：肝肺綜合癥 + 一氧化氮��； 參考：《浙江大學(xué)》2008年碩士論文

【摘要】： 背景: 呼吸系統(tǒng)癥狀在失代償期肝病患者中是非常常見的,半數(shù)以上的患者有氣短的主訴。在過去的10多年里,肝硬化患者肺血管異常越來越受到重視,因?yàn)槿藗円庾R到這是影響肝移植患者生存率的重要臨床因素。當(dāng)肺內(nèi)血管擴(kuò)張影響到動脈氧合時(shí)就可認(rèn)為存在肝肺綜合征(hepatopulmonary syndrome,HPS),15%-20%接受肝移植評估的患者合并有HPS,HPS的存在增加肝硬化患者的死亡率并可進(jìn)一步加重門脈高壓。經(jīng)典的HPS定義為原發(fā)肝病、低氧血癥和肺內(nèi)血管擴(kuò)張的三聯(lián)征。 肺內(nèi)血管異常擴(kuò)張是肝肺綜合癥的基本病理變化,對伴有低氧血癥的嚴(yán)重肝病患者作尸檢可以發(fā)現(xiàn)肺毛細(xì)血管彌漫性擴(kuò)張,直徑從正常的8μm-15μm擴(kuò)張至20μm-50μm,甚至500μm。目前認(rèn)為這種血管擴(kuò)張的原因是肝功能損傷時(shí)血管擴(kuò)張因子和收縮因子之間的失衡所致。由于肝功能障礙時(shí)肝臟滅活能力下降,加之門體分流的存在使擴(kuò)血管物質(zhì)直接進(jìn)入肺循環(huán),從而導(dǎo)致肺內(nèi)擴(kuò)血管物質(zhì)的增多;同時(shí)縮血管物質(zhì)含量下降、活性降低,或者肺血管內(nèi)皮對血管收縮因子的敏感性降低,使原本關(guān)閉的無功能肺毛細(xì)血管前交通支開放,從而導(dǎo)致本來正常的低氧性肺血管收縮功能發(fā)生障礙。常見的血管活性物質(zhì)有:一氧化氮、內(nèi)皮素、一氧化碳、腫瘤壞死因子等,這些物質(zhì)對HPS的發(fā)生、發(fā)展起重要的作用。 大鼠慢性膽管結(jié)扎(chronic bile duct ligation,CBDL)是目前復(fù)制人HPS病理生理特征的唯一模型,與其他常用的肝硬化或門脈高壓動物模型(如硫代乙酰胺、門脈部分結(jié)扎方法)相比,后者不伴有HPS形成。 目的: 大鼠慢性膽管結(jié)扎(CBDL)是目前復(fù)制人HPS病理生理特征的唯一模型。本實(shí)驗(yàn)的目的就是研究大鼠肝肺綜合征模型的建立及其病理生理演變過程,進(jìn)一步闡明肝肺綜合征的發(fā)病機(jī)制,為肝肺綜合征的治療提供新的理論基礎(chǔ)和治療切入點(diǎn)。 方法: 采用Sprague-Dawley大鼠,慢性膽管結(jié)扎(CBDL)方法制備HPS動物模型,共36只,隨機(jī)分為假手術(shù)組(Sham),2周組(2wk)和5周組(5wk)。采用病理染色觀察肝硬化形成及肺血管擴(kuò)張情況,血?dú)夥治鰴z測動脈血氧分壓從而驗(yàn)證造模情況。應(yīng)用比色法檢測血漿及肺組織中一氧化氮(NO),應(yīng)用ELISA法檢測血漿及肺組織中內(nèi)皮素-1(ET-1)及腫瘤壞死因子-α(TNF-α)水平。 統(tǒng)計(jì)學(xué)處理用EXCEL軟件完成,計(jì)量資料數(shù)據(jù)表示方式以平均值±標(biāo)準(zhǔn)差(Mean±SD),兩組計(jì)量資料采用非獨(dú)立樣本t檢驗(yàn)。P＜0.05為差異有統(tǒng)計(jì)學(xué)顯著性意義。 結(jié)果: 病理觀察顯示CBDL 2wk時(shí)肝纖維化形成,5wk時(shí)肝硬化形成,肺血管隨時(shí)間變化逐漸擴(kuò)張。血?dú)夥治鲲@示CBDL 2wk組和5wk組肺泡.動脈氧分壓差與假手術(shù)組相比均有顯著升高,證明通過CBDL成功復(fù)制了HPS模型。CBDL組血漿及肺組織中NO、ET-1含量均升高,與假手術(shù)組比較有顯著性差異。CBDL組血漿中TNF-α含量升高,與假手術(shù)組比較有顯著性差異。 結(jié)論: CBDL大鼠可較好的復(fù)制HPS模型用于實(shí)驗(yàn)研究。血漿及肺組織中NO、ET-1及TNF-α水平增加可能HPS重要的發(fā)病機(jī)制之一。
[Abstract]:Background:
Respiratory symptoms are very common in patients with decompensated liver disease, and more than half of the patients have shortness of breath. Over the past 10 years, pulmonary vascular abnormalities in patients with cirrhosis are becoming more and more important, because people realize that this is an important clinical factor affecting the survival rate of patients with liver transplantation. Hepatopulmonary syndrome (HPS) is considered to exist when oxygen is combined. The patients with 15%-20% for liver transplantation are combined with HPS. The presence of HPS increases the mortality of the patients with cirrhosis and further aggravates the portal hypertension. The classic HPS is defined as the triple sign of primary liver disease, hypoxemia, and pulmonary vasodilatation.
Abnormal expansion of the blood vessels in the lungs is the basic pathological change of the hepatopulmonary syndrome. The diffuse expansion of the pulmonary capillaries can be found in patients with severe liver disease accompanied by hypoxemia. The diameter of the pulmonary capillary dilates from normal 8 UU M-15 to 20 m-50 mu m, or even 500 mu m.. The reason for this vascular expansion is the vasodilator factor at the time of liver function injury. Due to the imbalance between the contractile factors, the decrease of liver inactivation ability and the presence of portal body diffluence make the vasodilator directly enter the pulmonary circulation, which leads to the increase of the pulmonary vasodilator material, and the decrease in the content of the vasoconstrictor material, the decrease of the activity, or the sensitivity of the pulmonary vascular endothelium to the vasoconstrictor. Decrease, make the previously closed non functional pulmonary capillaries open, which leads to normal hypoxic pulmonary vasoconstrictor dysfunction. The common vasoactive substances are nitric oxide, endothelin, carbon monoxide, tumor necrosis factor and so on. These substances play an important role in the development of HPS.
Chronic bile duct ligation (chronic bile duct ligation, CBDL) is the only model that replicating the pathophysiological characteristics of human HPS at present. Compared with other commonly used liver cirrhosis or portal hypertensive animal models (such as thioacetamide and partial ligature of portal vein), the latter is not accompanied by HPS formation.
Objective:
Chronic bile duct ligation (CBDL) is the only model that replicating the pathophysiological characteristics of human HPS. The aim of this experiment is to study the establishment of rat hepato lung syndrome model and its pathophysiological evolution process, further elucidate the pathogenesis of Hepato lung syndrome, and provide a new theoretical basis and treatment entry point for the treatment of Hepato lung syndrome.
Method:
HPS animal models were prepared by Sprague-Dawley rats and chronic bile duct ligation (CBDL). A total of 36 animals were randomly divided into sham operation group (Sham), 2 weeks group (2wk) and 5 week group (5wk). Pathological staining was used to observe the formation of liver cirrhosis and pulmonary vasodilatation. Blood gas analysis was used to test arterial oxygen pressure to verify the model condition. Plasma colorimetric assay was used to detect plasma. And nitric oxide (NO) in lung tissue, the levels of endothelin -1 (ET-1) and tumor necrosis factor - alpha (TNF- alpha) in plasma and lung tissue were detected by ELISA.
The statistical treatment was completed by EXCEL software, and the data representation of the measurement data was mean standard deviation (Mean + SD). The two groups of measurement data were statistically significant with the non independent sample t test.P < 0.05.
Result:
Pathological observation showed the formation of liver fibrosis in CBDL 2wk, the formation of liver cirrhosis in 5wk, and the gradual expansion of the pulmonary vessels with time. The blood gas analysis showed that the CBDL 2wk group and the 5wk group had a significant increase in the difference of oxygen pressure from the sham operation group. It was proved that the NO of the plasma and lung tissue of the HPS model.CBDL group was successfully copied through CBDL, and the ET-1 content was increased. There was a significant difference between the sham operation group and the sham operation group. The plasma level of TNF- alpha in group.CBDL was higher than that in sham operation group.
Conclusion:
CBDL rats can better replicate the HPS model for experimental study. The increase of NO, ET-1 and TNF- alpha levels in plasma and lung tissue may be one of the important pathogenesis of HPS.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R563;R-332

【共引文獻(xiàn)】

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本文編號：2010288