本文選題：肝硬化 + 微循環(huán)障礙��； 參考：《廣西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:肝臟缺血再灌注損傷(hepatic ischemia reperfusion injury,IRI)是導(dǎo)致慢性肝纖維化相關(guān)肝病患者行肝部分切除術(shù)或肝臟移植術(shù)后肝功能衰竭的主要原因之一,如何無創(chuàng)性監(jiān)測(cè)并預(yù)防肝臟IRI有助于提高手術(shù)安全系數(shù)。本文旨在探討聲脈沖輻射力成像(Acoustic radiation force impulse,ARFI)技術(shù)對(duì)合并慢性肝纖維化實(shí)驗(yàn)兔肝臟缺血再灌注的診斷價(jià)值。材料和方法:采用給予健康成年新西蘭兔腹腔內(nèi)注射由CCL4與橄欖油按1:1配成的50%CCL4-橄欖油溶液0.3ml/kg的方式制作肝硬化模型,選用45只成功制成肝硬化模型的新西蘭兔隨機(jī)分為三組:假手術(shù)組(A組,n=15)、肝門阻斷組(B組,n=15)、肝門阻斷加左半肝切除組(C組,n=15)。假手術(shù)組(A組):開腹30min后關(guān)閉腹腔;B組:阻斷第一肝門30min后重新恢復(fù)入肝血流;C組:在B組的基礎(chǔ)上同時(shí)切除左半肝。建模完成后三組肝硬化兔分別運(yùn)用ARFI技術(shù)于肝門阻斷前、肝門阻斷30min后再灌注0h、1h、6h、24h和48h六個(gè)時(shí)間點(diǎn)測(cè)量實(shí)驗(yàn)兔肝右葉實(shí)質(zhì)相同部位的肝組織剪切波速度SWV,同時(shí)檢測(cè)血清天冬氨酸氨基轉(zhuǎn)移酶(AST)、丙氨酸基轉(zhuǎn)移酶(ALT)的水平評(píng)估肝功能。將各個(gè)時(shí)間點(diǎn)切取的肝組織標(biāo)本經(jīng)10%甲醛液固定、HE染色后光鏡下觀察病理改變,并計(jì)算組織形態(tài)學(xué)總積分。數(shù)據(jù)分析采取ANOVA進(jìn)行統(tǒng)計(jì)分析,不同區(qū)組內(nèi)兩兩對(duì)照采用隨機(jī)區(qū)組方差分析,ARFI測(cè)值SWV與血清ALT、AST水平和組織形態(tài)學(xué)積分的相關(guān)性應(yīng)用pearson相關(guān)分析;P0.05作為差異有顯著意義的檢驗(yàn)標(biāo)準(zhǔn)。結(jié)果:A組再灌注0h、再灌注1h、再灌注6h及再灌注24h四個(gè)時(shí)相的AFRI測(cè)值SWV、血清AST、ALT水平與缺血前的相比,差異無統(tǒng)計(jì)學(xué)意義(P0.05),B組和C組兩組在再灌注早期0h和1h的ARFI測(cè)值分別與其術(shù)前的相比,差異均具有統(tǒng)計(jì)學(xué)意義(P0.05),而其ALT、AST水平僅在再灌注后1h升高,與術(shù)前和再灌注后0h相比,差異具有統(tǒng)計(jì)學(xué)意義(P0.05),此時(shí)B組和C組實(shí)驗(yàn)兔肝細(xì)胞的病理學(xué)表現(xiàn)為肝細(xì)胞水腫,肝板變窄和少量炎性細(xì)胞浸潤(rùn),造成肝竇阻塞現(xiàn)象,提示缺血再灌注早期,肝血流恢復(fù)后造成肝微循環(huán)功能的損傷。在缺血再灌注6h時(shí),B組和C組AFRI測(cè)值SWV、血清AST、ALT水平進(jìn)一步升高,病理表現(xiàn)為肝細(xì)胞水腫加重呈氣球樣變性。在24h和48h時(shí)AFRI測(cè)值SWV、血清AST、ALT水平持續(xù)升高,在24h達(dá)最高峰,持續(xù)的缺血損傷最終導(dǎo)致肝細(xì)胞變性壞死,細(xì)胞萎縮,肝竇塌陷。從再灌注后0h至24h肝組織標(biāo)本的組織形態(tài)學(xué)評(píng)分隨著再灌注時(shí)間的延長(zhǎng)逐漸升高,兩兩比較,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。B、C組AFRI測(cè)值SWV在肝缺血再灌注后的各個(gè)時(shí)間點(diǎn)與肝組織的病理改變一致,pearson相關(guān)性分析顯示AFRI測(cè)值SWV與血清ALT、AST水平、病理組織形態(tài)學(xué)積分呈顯著正相關(guān)(P0.05)。結(jié)論:ARFI可以動(dòng)態(tài)的無創(chuàng)性監(jiān)測(cè)肝硬化兔肝臟IRI中的微循環(huán)障礙及組織缺血再灌注損傷程度,為臨床評(píng)估HIRI提供理論依據(jù)。
[Abstract]:Objective: hepatic ischemia reperfusion injury is one of the main causes of liver failure after partial hepatectomy or liver transplantation in patients with chronic hepatic fibrosis. How to non-invasive monitoring and preventing liver IRI is helpful to improve the safety factor of operation. The purpose of this study was to evaluate the diagnostic value of acoustic pulse radiography with acoustic radiation force impulse imaging (ARFI) in the diagnosis of hepatic ischemia and reperfusion in rabbits with chronic hepatic fibrosis. Materials and methods: the liver cirrhosis model was established by intraperitoneal injection of CCL4 and olive oil with 50L4 olive oil solution 0.3ml/kg, which was made up of 1:1 in healthy adult New Zealand rabbits. Forty-five New Zealand rabbits were randomly divided into three groups: sham operation group (group A), hepatic hilus occlusion group (group B), hepatic hilus occlusion group (group C) and left hemihepatectomy group (group C). Group A (sham operation group): group B (closed abdominal cavity after opening 30min): group C: after blocking 30min of the first hepatic hilus, the left half liver was resected simultaneously on the basis of group B. After modeling, three groups of cirrhotic rabbits were treated with ARFI technique before hepatic portal occlusion. The shear wave velocities of liver tissue in the same part of the right lobe of liver were measured at 6 h and 48 h after hepatic hilus occlusion and reperfusion for 0 h, 1 h, 6 h and 48 h, and the serum levels of aspartate aminotransferase (AST) and alanine transferase (alt) were measured to evaluate liver function. The pathological changes were observed under light microscope and the total histomorphology score was calculated after the liver tissue samples were fixed with 10% formaldehyde solution and stained with HE at each time point. ANOVA is used to analyze the data. The correlation between SWV and serum alt AST level and histomorphology score was analyzed by random block ANOVA and pearson correlation analysis (P0.05) was used as the test standard of significant difference. Results compared with those before ischemia, the levels of AFRI were measured at 0 h, 1 h, 6 h and 24 h after reperfusion in group 1: a, and the levels of alt in serum of group A were compared with those before ischemia. There was no significant difference in ARFI values between group B and group C at 0 h and 1 h after reperfusion, and there was significant difference between group B and group C before and after reperfusion, while the level of alt AST increased only 1 h after reperfusion, compared with preoperative and 0 h after reperfusion. The difference was statistically significant (P 0.05). The pathological manifestations of hepatocytes in group B and group C were hepatocyte edema, narrowing of liver plate and infiltration of a few inflammatory cells, which caused hepatic sinusoidal obstruction, suggesting early ischemia reperfusion. Liver microcirculation function is damaged after the recovery of hepatic blood flow. At 6h after ischemia and reperfusion, the AFRI values of group B and group C were measured, and the serum alt level of AST was further increased, and the pathological features were as follows: the edema of hepatocytes was aggravated as balloon degeneration. At 24h and 48h, the level of serum ASTV-alt increased continuously and reached the peak at 24h. The sustained ischemic injury resulted in hepatocyte degeneration and necrosis, cell atrophy and sinusoidal collapse. From 0 h to 24 h after reperfusion, the histomorphologic scores of liver tissue increased with the prolongation of reperfusion time. The difference was statistically significant (P 0.05). The AFRI values of group C were consistent with the pathological changes of liver tissue at different time points after hepatic ischemia-reperfusion. The results of Pearson correlation analysis showed that there was a significant positive correlation between the SWV measured by AFRI and the level of alt AST in serum, and there was a significant positive correlation between the histopathological score and pathological tissue morphology score (P 0.05). Conclusion the microcirculation disturbance and the degree of ischemia reperfusion injury in liver IRI of cirrhotic rabbits can be dynamically monitored by WARFI, which provides a theoretical basis for clinical evaluation of HIRI.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R575.2;R445.1

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