【摘要】：眾多人體器官中,唯獨(dú)肝臟具有強(qiáng)大的修復(fù)與再生功能,深入闡明這種再生功能的機(jī)制有利于治療各種肝臟疾病。目前研究認(rèn)為肝再生(Liver regeneration)是一個(gè)非常復(fù)雜但受精確調(diào)控的過(guò)程,并把涉及其中的機(jī)制與因子主要分為三類：細(xì)胞因子信號(hào)通路、生長(zhǎng)因子信號(hào)通路和代謝網(wǎng)絡(luò)信號(hào)通路。已有研究報(bào)道基質(zhì)金屬蛋白酶-9(matrix metalloproteinase-9, MMP-9)在肝再生中扮演極其重要的積極角色,但是其中相關(guān)機(jī)制尚未完全明了。本次研究利用MMP-9敲除鼠,通過(guò)建立百分之七十肝切除模型來(lái)探討MMP-9調(diào)控表皮生長(zhǎng)因子受體(epidermal growth factor receptor, EFGR)信號(hào)通路在肝再生中的作用及其具體機(jī)制。方法：肝切除模型分為以下三組：1.1假手術(shù)組(施行開(kāi)關(guān)腹手術(shù))；1.2對(duì)照組(野生型小鼠建立肝切除模型)；1.3敲除組(MMP-9敲除鼠建立肝切除模型)。術(shù)后在相應(yīng)時(shí)間點(diǎn)采血取肝,檢測(cè)肝再生情況、EGFR配體、EGFR信號(hào)通路下游蛋白表達(dá)水平等。結(jié)果：MMP-9敲除小鼠較野生型小鼠在肝切除術(shù)后：肝再生延遲,早期EGFR配體雙調(diào)蛋白(Amphiregulin, AR)和肝素結(jié)合型表皮生長(zhǎng)因子(heparin-binding epidermal growth factors, HB-EGF)表達(dá)下調(diào),EGFR激活延遲。同時(shí)EGFR下游信號(hào)轉(zhuǎn)導(dǎo)與轉(zhuǎn)錄激活因子-3(Signal transducer and activator of transcription-3, STAT3),核因子κB (NF-κB),細(xì)胞周期蛋D1(cyclinD1)表達(dá)與EGFR一致下調(diào)。結(jié)論：MMP-9在肝再生中的重要作用是通過(guò)調(diào)控EGFR配體來(lái)影響EGFR信號(hào)通路的激活,從而進(jìn)一步影響細(xì)胞增生信號(hào)。
[Abstract]:Among many human organs, only the liver has strong repair and regeneration function, which is beneficial to the treatment of various liver diseases. At present, it is considered that liver regeneration (Liver regeneration) is a very complex but accurately regulated process, and the mechanisms and factors involved in it are mainly divided into three categories: cytokine signal pathway, growth factor signal pathway and metabolic network signal pathway. It has been reported that matrix metalloprotease-9 (matrix metalloproteinase-9, MMP-9) plays an important and active role in liver regeneration, but the related mechanisms are not yet fully understood. In this study, MMP-9 knockout mice were used to establish a 70% hepatectomy model to investigate the role of MMP-9 in regulating (epidermal growth factor receptor, EFGR) signaling pathway of epidermis growth factor receptor in liver regeneration and its specific mechanism. Methods: the hepatectomy model was divided into the following three groups: 1.1. false operation group (open abdominal operation), 1.2control group (wild type mice established hepatectomy model), 1.3knockout group (MMP-9 knockout mice established hepatectomy model). The liver was collected at the corresponding time point after operation to detect liver regeneration, EGFR ligands and the expression of downstream proteins in EGFR signaling pathway. Results: compared with wild type mice, MMP-9 knockout mice delayed liver regeneration and down-regulated the expression of EGFR ligand biregulatory protein (Amphiregulin, AR) and heparin binding epidermis growth factor (heparin-binding epidermal growth factors, HB-EGF) in early stage. EGFR activation delay. At the same time, the expression of signal transduction and transcription activating factor-3 (Signal transducer and activator of transcription-3, STAT3, nuclear factor kappa B (NF- kappa B) and cell cycle egg D1 (cyclinD1) downstream of EGFR were down-regulated with EGFR. Conclusion: the important role of MMP-9 in liver regeneration is to regulate EGFR ligands to affect the activation of EGFR signaling pathway, thus further affecting cell proliferation signal.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R657.3

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