【摘要】：目的探討內質網應激在四氯化碳(CCl4)誘導的小鼠急性肝損傷中的變化及作用機制。方法C57BL/6小鼠30只,隨機分為模型組和對照組各15只,模型組給予20%CCl4(0.1 m L/10 g)腹腔注射制備小鼠急性肝損傷模型,對照組給予橄欖油溶液腹腔注射(0.1 m L/10 g)作為正常對照。采用病理染色觀察小鼠肝組織病理形態(tài)學和肝細胞內質網應激相關蛋白以及凋亡蛋白的表達情況,采用蛋白質印跡法測定小鼠肝臟內質網應激相關蛋白以及凋亡相關蛋白的表達變化趨勢。結果 CCl4腹腔注射后8 h,模型組小鼠肝臟出現(xiàn)明顯的損傷,肝組織GRP78蛋白以及cleaved caspase-12表達量顯著升高(P0.05),cleaved caspase-3表達量亦顯著升高(P0.05);TUNEL法檢測結果均顯示模型組肝臟有嚴重損傷,大量肝細胞發(fā)生凋亡,凋亡指數(shù)較對照組明顯升高(P0.05),而PCNA染色顯示模型組肝細胞增殖指數(shù)明顯少于對照組(P0.05);相蛋白質印跡顯示,模型組內質網應激相關蛋白以及凋亡蛋白表達量均明顯升高,同時伴有線粒體細胞色素c的釋放,而促細胞增殖蛋白p-Akt、PCNA表達量明顯降低。結論內質網應激反應介導的線粒體細胞凋亡通路參與了CCl4誘導的小鼠急性肝損傷的發(fā)病過程。
[Abstract]:Objective To investigate the changes and mechanism of endoplasmic reticulum stress in acute liver injury induced by carbon tetrachloride (CCl4). Methods Thirty C57BL/ 6 mice were randomly divided into two groups: model group and control group. The model group was given 20% CCl4 (0.1 m L/ 10 g) to prepare acute liver injury model of mice. The control group was given an intraperitoneal injection of olive oil solution (0.1 m L/ 10 g) as the normal control. The expression of endoplasmic reticulum stress-related protein and apoptosis protein in the liver of mice was observed by pathological staining, and the expression trend of the related protein and apoptosis-related protein in the liver of mice was determined by Western blot. Results The expression of the liver tissue GRP78 protein and the clear caspase-12 increased significantly (P0.05). The results of the TUNEL method showed that the liver of the model group was severely damaged. In the model group, the expression of the endoplasmic reticulum stress-related protein and the apoptosis protein of the model group was significantly higher than that in the control group (P0.05). At the same time, the release of cytochrome c was accompanied by the release of cytochrome c, and the expression of p-Akt and PCNA in the pro-cell proliferation was significantly lower. Conclusion Endoplasmic reticulum stress-mediated apoptosis pathway is involved in the pathogenesis of acute liver injury induced by CCl4.
【作者單位】： 廣東省羅定市人民醫(yī)院消化內科;中山大學附屬第三醫(yī)院消化內科;
【分類號】：R575

【共引文獻】

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