自噬现象在肝纤维化和肝切除时的表现形式

Autophagy in Fibrotic and Postoperative Remnant Liver in Rat

目的了解肝纤维化和肝切除时同肝脏再生并行的自噬现象的表现和差别。方法雄性Wistar大鼠随机分成对照组、肝纤维化组和肝切除组;采用四氯化碳复合法制作肝纤维化大鼠模型,病理证实肝纤维化后,于诱导的第5周取材;采用改良70%肝切除法制作大鼠肝切除模型,于术后18 h取材。观察大鼠一般状况,定量比较血清肝功能指标的变化,用光镜、透射电镜观察肝细胞形态学改变及肝脏再生差别;利用透射电镜数据定量分析自噬现象的变化。结果肝纤维化组血清总蛋白、白蛋白较对照组显著降低（P〈0.01）,增殖细胞核抗原（PCNA）指数为85%-95%,自噬现象指数较对照组下降19%（P〈0.05）;肝切除组丙氨酸氨基转移酶、天冬氨酸氨基转移酶较对照组显著升高（P〈0.01）,PCNA指数为20%-30%,自噬现象指数较对照组下降95%（P〈0.01）;肝纤维化组和肝切除组自噬体内容物及形态发生显著改变。结论自噬现象在肝切除和肝纤维化代偿过程中均有不同程度的削弱,但二者表现形式不同,进一步对自噬现象的调节有可能促进和帮助术后剩余肝脏功能的恢复。

Objective To evaluate the characteristics of autophagy in fibrotic and postoperative remnant liver.Methods Male Wistar rats were randomly divided into three groups： control group;fibrosis group,which received the solution of CCl4 in oil twice a week for 5 weeks;and hepatectomy group,which underwent 70% hepatectomy.Liver tissues and plasma were harvested 18 hours after the surgery.The rats＇ general conditions and plasma liver function were observed.Histopathological characteristics and regeneration were observed with microscope and transmission electron microscope.Qualitative analysis of autophagosome was made base on the data from transmission electron microscope.Results Compared with the control group,plasma total protein and albumin level significantly decreased in the fibrosis group（P〈0.01）.Proliferating cell nuclearantigen（PCNA） index was 85%-95% in the fibrosis group.Plasma alanine aminotransferase and aspartate aminotransferase levels significantly increased in the hepatectomy group compared with the control group（P〈0.01）,while the autophagical index significantly decreased in both the fibrosis group and hepatectomy group compared with the control group（-95%,P〈0.01;-19%,P〈0.05,respectively）.PCNA index was 20%-30% in the hepatectomy group.Conclusions Autophagy is weakened after fibrosis and hepatectomy,although it differs between these two processes.Proper regulation of autophagy may help facilitate the recovery of the residual liver function after hepatectomy.