CAJ | 학술논문

目的：探讨内质网应激在四氯化碳（CCl4）诱导的小鼠急性肝损伤中的变化及作用机制。方法C57BL／6小鼠30只，随机分为模型组和对照组各15只，模型组给予20％ CCl4（0．1 mL／10 g）腹腔注射制备小鼠急性肝损伤模型，对照组给予橄榄油溶液腹腔注射（0．1 mL／10 g）作为正常对照。采用病理染色观察小鼠肝组织病理形态学和肝细胞内质网应激相关蛋白以及凋亡蛋白的表达情况，采用蛋白质印迹法测定小鼠肝脏内质网应激相关蛋白以及凋亡相关蛋白的表达变化趋势。结果CCl4腹腔注射后8 h，模型组小鼠肝脏出现明显的损伤，肝组织 GRP78蛋白以及 cleaved caspase －12表达量显著升高（P ＜0．05），cleaved caspase －3表达量亦显著升高（P ＜0．05）；TUNEL 法检测结果均显示模型组肝脏有严重损伤，大量肝细胞发生凋亡，凋亡指数较对照组明显升高（P ＜0．05），而 PCNA 染色显示模型组肝细胞增殖指数明显少于对照组（P ＜0．05）；相蛋白质印迹显示，模型组内质网应激相关蛋白以及凋亡蛋白表达量均明显升高，同时伴有线粒体细胞色素 c 的释放，而促细胞增殖蛋白p －Akt、PCNA 表达量明显降低。结论内质网应激反应介导的线粒体细胞凋亡通路参与了 CCl4诱导的小鼠急性肝损伤的发病过程。
목적：탐토내질망응격재사록화탄（CCl4）유도적소서급성간손상중적변화급작용궤제。방법C57BL／6소서30지，수궤분위모형조화대조조각15지，모형조급여20％ CCl4（0．1 mL／10 g）복강주사제비소서급성간손상모형，대조조급여감람유용액복강주사（0．1 mL／10 g）작위정상대조。채용병리염색관찰소서간조직병리형태학화간세포내질망응격상관단백이급조망단백적표체정황，채용단백질인적법측정소서간장내질망응격상관단백이급조망상관단백적표체변화추세。결과CCl4복강주사후8 h，모형조소서간장출현명현적손상，간조직 GRP78단백이급 cleaved caspase －12표체량현저승고（P ＜0．05），cleaved caspase －3표체량역현저승고（P ＜0．05）；TUNEL 법검측결과균현시모형조간장유엄중손상，대량간세포발생조망，조망지수교대조조명현승고（P ＜0．05），이 PCNA 염색현시모형조간세포증식지수명현소우대조조（P ＜0．05）；상단백질인적현시，모형조내질망응격상관단백이급조망단백표체량균명현승고，동시반유선립체세포색소 c 적석방，이촉세포증식단백p －Akt、PCNA 표체량명현강저。결론내질망응격반응개도적선립체세포조망통로삼여료 CCl4유도적소서급성간손상적발병과정。
Objective To investigate the change and mechanism of endoplasmic reticulum (ER) stress in acute liver injury induced by carbon tetrachloride (CCl4 ) in mice.Methods Thirty C57BL/6 mice were randomly allocated to treatment group and control group (n =15).Treatment group was given CCl 4 (20%/0.1 mL/10 g) intraperitoneally to es-tablish acute liver injury models, and olive oil was given as placebo in the control group .The expressions of ER stress -related proteins and apoptotic proteins in the liver were determined by pathological staining .The trends of ER stress -re-lated proteins and apoptotic proteins were also analyzed by Western blot .Results According to pathological analysis , that administration of CCl4 caused marked hepatic injury , characterized by significant expressions of ER stress -related pro-teins and apoptotic proteins combined with a remarkable reduction of proliferative proteins PCNA .TUNEL staining and PCNA staining showed that significant increasing apoptotic cells and reduced proliferative cells , respectively, when com-pared with the control group (P <0.05).By the same time, Western blot analysis also demonstrated that administration of CCl4 to mice caused significant elevated expression of ER stress -related proteins and apoptotic proteins , accompanied with the release of mitochondrial cytochrome c and obvious repression of proliferative proteins , such as p -Akt and PCNA. Conclusion ER stress -mediated mitochondrial apoptotic pathway plays an important role in the pathogenesis of CCl 4 -induced acute liver injury in mice.