关键词: 肝纤维化, 磷脂酰肌醇-3激酶/蛋白激酶, 内质网应激, 葡萄糖调节蛋白78, 生长停滞及DNA损伤基因

Abstract: Objective To observe the changes of PI3K/Akt signaling pathway and endoplasmic reticulum stress related protein GRP78 and CHOP in CCl4 induced liver fibrosis and to explore their effects on hepatic fibrosis. Methods Thirty SD rats were randomly divided into normal control group, 4 and 8 weeks liver fibrosis group (hypodermic injection of 40% CCl4). Pathological changes of liver tissue was observed by HE staining. The techniques of real-time fluorescence quantitative PCR was applied to detect mRNA of GRP78 and CHOP in liver. Detected expression of Akt1, phospho-Akt1, GRP78 and CHOP protein by western blot. Meanwhile, the cell apoptosis in liver was detected by TUNEL. Results Compared with the normal control group, GRP78 and CHOP mRNA and protein in 4 and 8 weeks liver fibrosis group was increased(P＜0.05), while expression of Akt1, phospho-Akt1 in 4 and 8 weeks liver fibrosis group was lower than that in normal control group(P＜0.05). Compared with the normal control group, the apoptosis of hepatocytes in 4 and 8 weeks liver fibrosis group was elevated (P＜0.05). Conclusions PI3K/Akt signaling pathway and endoplasmic reticulum stress may play important roles in apoptosis of hepatocytes in rats with hepatic fibrosis.

Key words: hepatic fibrosis, PI3K/Akt, endoplasmic reticulum stress, GRP78, CHOP