本文關(guān)鍵詞：新西蘭兔四氯化碳肝硬化模型的建立與黃曲霉毒素B1對該模型肝臟急性損傷作用的觀察　出處：《廣西醫(yī)科大學(xué)》2008年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 新西蘭兔 CCl_4 肝硬化 逆轉(zhuǎn) 黃曲霉毒素

【摘要】： 背景我們發(fā)現(xiàn)黃曲霉毒素B1(Aflatoxin B1,AFB1)對肝臟的損傷作用有個體差異;肝臟的基礎(chǔ)疾病可能影響AFB1的體內(nèi)代謝過程及其毒性作用從而影響個體腫瘤發(fā)生的危險性。因此探討病毒性肝炎患者中AFB1暴露所造成的肝損傷可能有助于闡明肝炎病毒與化學(xué)毒物協(xié)同致癌的作用機制。 目的本課題擬通過四氯化碳化學(xué)損傷處理建立新西蘭兔肝硬化模型,觀察該肝硬化模型建立后的穩(wěn)定性,并初步觀察AFB1對該模型的急性損傷作用,為下階段利用該動物模型進行原發(fā)性肝癌的發(fā)病機制研究打下基礎(chǔ)。 方法第一階段,將雄性新西蘭兔24只隨機分為A、B、C、D組,分別給予安慰劑,低、中、高劑量的四氯化碳(Carbon Tetrachloride,CCl_4)觀察其體重(body weight,BW)、總蛋白(total protein,TP)、白蛋白(albumin,Alb)、球蛋白(globulin,Glo)、丙氨酸氨基轉(zhuǎn)移酶(alanine aminotransferase,ALT)、天門冬氨酸氨基轉(zhuǎn)移酶(aspartate aminotransferase,AST)、γ-谷氨酰轉(zhuǎn)移酶(γ-glutamyltransferase,G-GT)、白細胞(white blood cell,WBC)、紅細胞(red blood cell,RBC)、血紅蛋白(hemoglobin,HGB)和血小板(platelet,PLT)的變化,并定期進行隨機抽樣肝活檢,直到活檢發(fā)現(xiàn)肝硬化時停止給藥;第二階段,繼續(xù)觀察8周,檢測其BW、TP、Alb、Glo、ALT、AST、G-GT、WBC、RBC、HGB和PLT,第3、5、8周時進行抽樣肝活檢觀察肝硬化是否逆轉(zhuǎn);第三階段,在觀察第8周末將存活的新西蘭兔平均分為兩組,一組給予0.5mg/kg劑量的AFB1處理,觀察其對新西蘭兔的肝功能和血常規(guī)指標(biāo)的影響。 結(jié)果第一階段,在第2-3周,C組有3只新西蘭兔死亡,D組有5只新西蘭兔死亡,在第10周,病理活檢顯示,A組新西蘭兔全為S0期,B組新西蘭兔有3只為S4期,2只新西蘭兔為S3期;第二階段,在第3周,病理活檢示,B組5只新西蘭兔肝纖維化分期與第一階段第10周比較有統(tǒng)計學(xué)差異(P＜0.05),肝纖維化程度均有不同程度的減輕;第三階段,0.5mg/kgAFB1處理后兩小時,新西蘭兔的TP、Alb、Glo、ALT、AST、G-GT、WBC、RBC、HGB和PLT無明顯改變(P＞0.05)。 結(jié)論按0.3ml/kg劑量給予新西蘭雄性白兔皮下注射橄欖油與CCl_4按1:1配成50%的CCl_4溶液,每3天一次,連續(xù)10周,可以建成肝硬化模型。用本方法建成的肝硬化模型不穩(wěn)定,在撤藥后至多3周均發(fā)生不同程度的逆轉(zhuǎn),其肝功能和血常規(guī)各項指標(biāo)都恢復(fù)到給藥前水平。因此要獲得穩(wěn)定的肝硬化模型必須持續(xù)給藥。給予該模型動物腹腔內(nèi)注射0.5mg/kg劑量的AFB1,兩小時內(nèi)檢查肝功能和血常規(guī)無明顯異常。
[Abstract]:Background We found that the effects of aflatoxin B1 (AFB1) on liver injury were different in individuals. The underlying diseases of the liver may affect the metabolic process and toxicity of AFB1 in vivo and thus affect the risk of individual tumorigenesis. Therefore, to explore the possibility of liver damage caused by AFB1 exposure in patients with viral hepatitis. It is helpful to clarify the mechanism of synergistic carcinogenesis between hepatitis virus and chemical poison. Objective to establish the liver cirrhosis model of New Zealand rabbits by chemical injury of carbon tetrachloride and to observe the stability of the model and the acute injury effect of AFB1 on the model. It will lay a foundation for the study of the pathogenesis of primary liver cancer by using the animal model in the next stage. Methods in the first stage, 24 male New Zealand rabbits were randomly divided into two groups. High dose carbon Tetrachloride CCL _ (4) was used to observe the weight of carbon tetrachloride (BW). Total protein (TP), Albumin (Alb), globulin (Glo.). Alanine aminotransferase (alt). Aspartate aminotransferase (AST). 緯 -glutamyltransferase G-GTN (white blood cell). The changes of red blood cell blood, hemoglobin (HGB) and platelet platelet (PLT) were observed. Random liver biopsy was carried out regularly until the liver cirrhosis was detected by biopsy. In the second stage, eight weeks of observation were carried out to detect its BWN TPN, Alb, Glot, ASTG-GTN, WBC, RBCU, HGB and PLT, No. 3, 5. Liver biopsy was performed at 8 weeks to observe whether liver cirrhosis was reversed or not. In the third stage, the surviving New Zealand rabbits were divided into two groups at the end of the 8th week. One group was treated with 0.5 mg / kg AFB1. To observe its effect on liver function and blood routine indexes of New Zealand rabbits. Results in the first stage, 3 New Zealand rabbits died in group C at 2-3 weeks and 5 New Zealand rabbits in group D died. At the 10th week, pathological biopsy showed that all New Zealand rabbits in group A were S0. In group B, there were 3 New Zealand rabbits with stage S4 and 2 New Zealand rabbits with stage S3. In the second stage, at the third week, pathological biopsy showed that there was a significant difference in hepatic fibrosis stage between group B and the first 10 weeks (P < 0.05). The degree of hepatic fibrosis was alleviated in different degree. Two hours after the treatment of 0.5 mg / kg AFB1 in the third stage, New Zealand rabbits were treated with TTP Alb, Glob, GGTG, WBC1 and RBC. There was no significant change in HGB and PLT (P > 0.05). Conclusion New Zealand male rabbits were subcutaneously injected with olive oil at a dose of 0.3 ml / kg to form 50% CCl_4 solution with CCl_4 at 1: 1, once every 3 days for 10 weeks. The liver cirrhosis model established by this method is unstable and reversed in varying degrees at most 3 weeks after withdrawal. The liver function and blood routine were all recovered to the level before administration, so the stable liver cirrhosis model must be continuously administered. The model animal was given intraperitoneal injection of 0.5 mg / kg AFB1. There was no obvious abnormality in liver function and blood routine examination within two hours.
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2008
【分類號】：R575.2;R-332

【引證文獻】

相關(guān)博士學(xué)位論文 前1條

1 秦哲;黃芪發(fā)酵后主要有效成分變化分析及多糖對大鼠實驗性肝纖維化影響[D];甘肅農(nóng)業(yè)大學(xué);2012年

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本文編號：1421895