CAJ | 학술논문

目的：探讨内质网应激( ERS)标志性蛋白天冬氨酸特异性半胱氨酸蛋白酶12( Caspase-12)在大鼠肝纤维化形成与逆转恢复病程中的作用。方法建立四氯化碳( CCl4)诱导大鼠肝纤维化模型，苏木精-伊红染色和Masson胶原纤维染色观察肝脏病理组织学改变；免疫组化法检测肝组织肝纤维化标志性蛋白α平滑肌肌动蛋白(α-SMA)以及钙激活蛋白酶( Calpain)的表达；Western blot检测不同时期肝脏组织中 Calpain、Cleaved-Caspase-12和 Cleaved-Caspase-3蛋白表达变化。结果肝脏病理组织学检测提示肝纤维化逆转恢复模型成功。免疫组化结果显示，与正常组比较，模型组大鼠肝脏组织中α-SMA和Calpain抗原阳性细胞明显增多、着色明显加深，且多分布在肝实质肝细胞区域。逆转恢复期，α-SMA抗原表达阳性细胞与模型组比较逐渐下降。Calpain抗原表达阳性细胞主要分布在肝脏的小叶中央静脉、汇管区、肝窦间隙等部位。 Western blot结果显示，模型组肝脏 Calpain、Cleaved-Caspase-12和 Cleaved-Caspase-3蛋白的表达与正常组相比显著升高。与模型组相比，逆转恢复2、4和8周组肝组织Calpain、Cleaved-Caspase-12和Cleaved-Caspase-3蛋白的表达降低，但仍高于正常组。结论 ERS标志性蛋白Caspase-12诱导的细胞凋亡存在于大鼠肝纤维化病程中，可能与肝纤维化的发生、发展和恢复逆转密切相关。
목적：탐토내질망응격( ERS)표지성단백천동안산특이성반광안산단백매12( Caspase-12)재대서간섬유화형성여역전회복병정중적작용。방법건립사록화탄( CCl4)유도대서간섬유화모형，소목정-이홍염색화Masson효원섬유염색관찰간장병리조직학개변；면역조화법검측간조직간섬유화표지성단백α평활기기동단백(α-SMA)이급개격활단백매( Calpain)적표체；Western blot검측불동시기간장조직중 Calpain、Cleaved-Caspase-12화 Cleaved-Caspase-3단백표체변화。결과간장병리조직학검측제시간섬유화역전회복모형성공。면역조화결과현시，여정상조비교，모형조대서간장조직중α-SMA화Calpain항원양성세포명현증다、착색명현가심，차다분포재간실질간세포구역。역전회복기，α-SMA항원표체양성세포여모형조비교축점하강。Calpain항원표체양성세포주요분포재간장적소협중앙정맥、회관구、간두간극등부위。 Western blot결과현시，모형조간장 Calpain、Cleaved-Caspase-12화 Cleaved-Caspase-3단백적표체여정상조상비현저승고。여모형조상비，역전회복2、4화8주조간조직Calpain、Cleaved-Caspase-12화Cleaved-Caspase-3단백적표체강저，단잉고우정상조。결론 ERS표지성단백Caspase-12유도적세포조망존재우대서간섬유화병정중，가능여간섬유화적발생、발전화회복역전밀절상관。
Objective To detect the effect of endoplasmic reticulum stress ( ERS)-related protein Caspase-12 in rat liver fibrosis and spontaneous reversal process. Methods Liver fibrosis model was induced by CCl4 in rats, the protein expressions of Calpain andα-SMA were detected by immunohistochemical staining. The protein expressions of Calpain,Cleaved-Caspase-12 and Cleaved-Caspase-3 in liver tissue were measured by Western blot. Results Immunohistochemistry results showed that compared with the normal group,α-SMA and calpain antigen-positive cells of rat liver tissue in model group were significantly increased, distributing in liver parenchymal area. Com-pared with model group,in recovery model,α-SMA antigen-positive cells decreased. Calpain antigen-positive cells were mainly distributed in the liver lobule central vein, portal area, sinusoidal gap and other parts. Western blot results showed that compared with the control group, expressions of Calpain, Cleaved-Caspase-12 and Cleaved-Caspase-3 were significantly enhanced in the model group. Compared with the model group, expressions of Cal-pain,Cleaved-Caspase-12 and Cleaved-Caspase-3 were decreased in spontaneous recovery after 2, 4 and 8 weeks. Conclusion ERS-related protein Caspase-12 might be related to the progression and regrossion of liver fibrosis.