Effect of single high-dose irradiation on rat hepatic stellate cells, transforming growth factor β, and PI3K/Akt signaling pathway molecule p-Akt (S473)

Abstract

Objective To investigate the effect of single high-dose irradiation on rat hepatic stellate cells (HSCs), transforming growth factor β(TGF-β), and PI3K/Akt signaling pathway. Methods A total of 40 healthy male Sprague-Dawley rats were randomly divided into model group (30 rats) and control group (10 rats). The rats in the model group were given single 6 MV X-ray irradiation of the right liver at a dose of 30 Gy, and those in the control group were given sham irradiation with the same method. At 3, 5, and 10 days after irradiation, 10 rats in the model group and 3-4 rats in the control group were randomly selected to measure the changes in the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALP), alkaline phosphatase (ALP), total bilirubin (TB), and direct bilirubin (DB). Hematoxylin-eosin (HE) staining and Masson staining were applied for liver tissues to observe the pathomorphological changes, and immunohistochemistry was used to measure the expression of transforming growth factor-beta 1(TGF-β1), alpha-smooth muscle actin (α-SMA), and p-Akt (S473) in liver tissues. Results At 3, 5, and 10 days after irradiation, the model group showed increases in the serum levels of AST, ALT, ALP, TB, and DB, and had significantly higher serum levels of these indices than the control group. The HE staining and Masson staining showed that compared with the control group, the rats with acute liver injury induced by radiation in the model group had a significant formation of collagen fibers around the hepatic sinusoids. Immunohistochemistry showed that with the prolonged time after irradiation, the expression of TGF-β1, α-SMA, and p-Akt (S473) was gradually enhanced after irradiation, and IPP analysis showed significant differences between the two groups (P<0.000). Conclusions During the process of acute radiation-induced liver injury induced by single high-dose irradiation, with the activation of HSCs, the secretion of TGF-β1 is increased and the PI3K/Akt signaling pathway is activated. Key words: Radiation induced liv er injury; Transforming growth factor beta; Hepatic stellate cells; Signal pathway