本文關(guān)鍵詞：前列腺素E_2對(duì)急性肝衰竭小鼠肝臟的保護(hù)作用及促肝再生作用的研究，由筆耕文化傳播整理發(fā)布。

        第一部分前列腺素E2對(duì)急性肝衰竭小鼠肝臟的保護(hù)作用研究目的：本研究通過(guò)建立對(duì)乙酰氨基酚(acetaminophen, APAP)誘導(dǎo)的小鼠急性肝衰竭模型,研究前列腺素E2(prostaglandin E2, PGE2)對(duì)APAP導(dǎo)致的急性肝衰竭小鼠肝臟的保護(hù)作用。方法：健康8周齡ICR小鼠,隨機(jī)分為模型對(duì)照組、PGE2治療組和正常對(duì)照組。正常對(duì)照組小鼠給予生理鹽水腹腔注射和無(wú)菌PBS皮下注射；模型對(duì)照組小鼠APAP腹腔注射造模后給予無(wú)菌PBS皮下注射治療；PGE2治療組小鼠APAP腹腔注射造模后給予dmPGE2皮下注射治療。各組小鼠造模后第12小時(shí)、24小時(shí)、48h處死采血檢測(cè)血清谷丙轉(zhuǎn)氨酶(alanine aminotransferase, ALT)和總膽紅素(total bilirubin, TBIL)濃度,取肝臟組織進(jìn)行病理檢查并對(duì)肝組織損傷程度進(jìn)行分級(jí)。結(jié)果：模型對(duì)照組小鼠血清ALT在造模后12h、24h、48h均顯著高于正常對(duì)照組(P<0.05)；造模后12h、24h PGE2治療組小鼠血清ALT低于同時(shí)間點(diǎn)模型對(duì)照組(P<0.05),48h兩組差別未達(dá)到統(tǒng)計(jì)學(xué)顯著性(P>0.05)。造模后12h模型對(duì)照組小鼠血清TBIL較正常對(duì)照組升高(P<0.05), PGE2治療組較模型對(duì)照組降低(P<0.05)；24h、48h各處理組間無(wú)明顯差異(P<0.05)。肝組織病理學(xué)檢查顯示模型對(duì)照組小鼠在造模后12h已經(jīng)出現(xiàn)了明顯的肝臟損害表現(xiàn),12h、24h、48h肝損傷分級(jí)分別為4.0±0.7級(jí)、3.8±0.8級(jí)、2.4±1.1級(jí)。PGE2治療組造模后12h、24h、48h肝損傷平均分級(jí)分別為1.4±0.5級(jí)、2.2±0.8級(jí)、1.2±0.4級(jí),與模型對(duì)照組相比明顯減輕(P<0.05)。結(jié)論：PGE2不但能減輕APAP所造成的肝損傷,還可以加快肝損傷的恢復(fù),具有開(kāi)發(fā)為治療急性肝衰竭的有效藥物的潛力。第二部分前列腺素E2對(duì)急性肝衰竭小鼠肝再生促進(jìn)作用及其與HGF、Wnt2及β-catenin關(guān)系的研究目的：通過(guò)觀察APAP誘導(dǎo)的肝衰竭小鼠肝臟再生情況及檢測(cè)HGF、Wnt2及β-catenin在肝臟的表達(dá)水平,研究PGE2對(duì)肝衰竭小鼠肝再生的影響,及HGF、 Wnt2及β-catenin在PGE2調(diào)節(jié)肝再生過(guò)程中所發(fā)揮的作用。方法：取各處理組小鼠造模后12h、24h、48h肝組織石蠟切片進(jìn)行增殖細(xì)胞核抗原(proliferating cell nuclear antigen, PCNA)免疫組化染色,以檢測(cè)肝細(xì)胞分裂增殖情況；用RT-PCR及Western Blot檢測(cè)肝臟組織中HGF、Wnt、β-catenin mRNA及蛋白水平的改變。結(jié)果：在造模后12h、24h,模型對(duì)照組小鼠肝臟PCNA陽(yáng)性率低于正常對(duì)照組,但差別未達(dá)到統(tǒng)計(jì)學(xué)顯著性(P>0.05),48h模型對(duì)照組小鼠肝臟PCNA陽(yáng)性率高于正常對(duì)照組(15.4±4.8%vs10.0±1.9%,P<0.05)；同時(shí)間點(diǎn)相比,PGE2治療組小鼠肝臟PCNA陽(yáng)性率均高于正常對(duì)照組和模型對(duì)照組,其中24h、48h差別達(dá)到統(tǒng)計(jì)學(xué)顯著性(P<0.05)。各時(shí)間點(diǎn)模型對(duì)照組小鼠與正常對(duì)照組小鼠相比,肝臟HGF和β-catenin mRNA表達(dá)無(wú)顯著差異(P>0.05); PGE2治療組小鼠肝臟HGF和β-catenin mRNA表達(dá)較模型對(duì)照組升高(P<0.05)。造模后12h PGE2治療組小鼠肝臟Wnt2mRNA表達(dá)高于模型對(duì)照組(P<0.05),但在24h、48h兩組相比無(wú)明顯差別(P>0.05)。12h、24h PGE2治療組小鼠HGF蛋白表達(dá)水平高于模型對(duì)照組,各組小鼠肝臟β-catenin、Wnt2蛋白水平表達(dá)改變不明顯。結(jié)論：PGE2具有促進(jìn)APAP導(dǎo)致的急性肝衰竭小鼠肝臟再生的作用,其促肝再生效應(yīng)可能與HGF和β-catenin作用相關(guān)。

    Part ⅠThe Role of Prostaglandin E2in Alleviating Liver Indury in Acute Liver Failure in MiceAims:To investigate the role of prostaglandin E2(PGE2) in alleviating acute liver injury induced by acetaminophen (APAP) in mice.Methods:Eight-week ICR mice were randomly divided into three groups:(1) the normal control group:normal mice treated with saline;(2) the liver failure group: APAP-induced liver failure mice treated by phosphate buffer saline; and (3) PGE2-treated group:APAP-induced liver failure mice treated by dmPGE2; The mice were killed and samples were obtained at12hours,24hours,48hours after APAP administration, respectively. Serum alanine aminotransferase (ALT) and total bilirubin (TBIL) were measured and sections of liver were prepared for histological examination.Results:The level of serum ALT of the liver failure group mice was elevated at12h,24h,48h after APAP administration comparing to normal mice; and it was lower in PGE2treated mice at12h and24h comparing to the live failure group (P<0.05), while there was no significant difference at48h (P>0.05). The level of serum TBIL of liver failure mice was elevated at12h after APAP administration comparing to normal mice whereas down-regulated in mice of PGE2-treated group(P<0.05); however, no significant difference were found among the three groups at24h and48h (P>0.05). Severe liver damage was observed at12h after APAP administration by histological examination, and the degree of liver injury of the mice in liver failure group at12h,24h,48h were4.0±0.7,3.8±0.8,2.4±1.1, respectively; while he degree of liver injury of the mice in PGE2-treated group at12h,24h,48h were1.4±0.5,2.2±0.8,1.2±0.4, respectively. The PGE2group showed slighter liver injury than the liver failure group (P<0.05).Conclusions:PGE2can alleviate APAP-induced acute liver injury in mice and facilitate the recovery of the liver. It might be a potential medication for treating liver failure. Part ⅡThe Effect of Prostaglandin E2in Liver Regeneration of Acute Liver Failure in Mice and the Correlationship with HGF, Wnt2and β-cateninAims:To investigate the effect of PGE2in enhancing liver regeneration in mice with APAP-induced acute liver failure and the role of HGF, Wnt2and β-catenin in regulation of liver regeneration by PGE2.Methods:Proliferating cell nuclear antigen (PCNA) which indicating the level of liver regeneration was evaluate by immunohistochemistry on sections of paraffin-embedded liver tissue. The expression of HGF, Wnt2and β-catenin was evaluated by reverse transcription-polymerase chain reaction and western blot.Results:The rate of PCNA-positive cells in liver of liver failure mice group was down-regulated at12h and24h after APAP administration comparing to normal group, but the difference did not reach the statistic significance (P>0.05); and it was up-regulated at48h (15.4±4.8%vs10.0±1.9%, P<0.05). Treatment of PGE2up-regulated the rate of PCNA-positive cells at24h and48after APAP administration respectively, comparing to other groups (P<0.05). The expression of HGF and (3-catenin mRNA was up-regulated in mice of PGE2-treated group comparing to liver failure group(P<0.05), while there was no significant difference between normal group and liver failure group(P>0.05). The expression of Wnt2mRNA was up-regulated in PGE2-treated group comparing to liver failure group at12h after APAP-administration(P<0.05). The level of β-catenin and Wnt2protein showed no changed by western blot; while the level of HGF protein was up-regulated in mice of PGE2-treated group comparing to liver failure group at12h and24h, respectively.Conclusions:PGE2was capable of enhancing liver regeneration in mice with APAP-induced acute liver failure and this effect might correlate to HGF and β-catenin.

前列腺素E_2對(duì)急性肝衰竭小鼠肝臟的保護(hù)作用及促肝再生作用的研究

縮略語(yǔ)表4-5中文摘要5-7Abstract7-8引言9-14    參考文獻(xiàn)10-14第一部分 前列腺素E_2對(duì)急性肝衰竭小鼠肝臟的保護(hù)作用研究14-29    前言14    材料與方法14-17    結(jié)果17-23    討論23-25    結(jié)論25    參考文獻(xiàn)25-29第二部分 前列腺素E_2對(duì)急性肝衰竭小鼠肝再生促進(jìn)作用及其與HGF、Wnt 及β-catenin關(guān)系的研究29-53    前言29    材料與方法29-40    結(jié)果40-46    討論46-48    結(jié)論48    參考文獻(xiàn)48-53綜述53-64    參考文獻(xiàn)57-64附錄64-67碩士期間發(fā)表的論文67-68致謝68-70

  本文關(guān)鍵詞：前列腺素E_2對(duì)急性肝衰竭小鼠肝臟的保護(hù)作用及促肝再生作用的研究，，由筆耕文化傳播整理發(fā)布。