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.
Corresponding Authors:
Bao Yongxing,Email:baoyx@vip.sina.com
Cite this article:
. Effect of single high-dose irradiation on rat hepatic stellate cells,transforming growth factor β,and PI3K/Akt signaling pathway molecule p-Akt (S473)[J]. Chinese Journal of Radiation Oncology, 2016, 25(3): 282-286.
. Effect of single high-dose irradiation on rat hepatic stellate cells,transforming growth factor β,and PI3K/Akt signaling pathway molecule p-Akt (S473)[J]. Chinese Journal of Radiation Oncology, 2016, 25(3): 282-286.
[1] Westbury CB,Yarnold JR.Radiation fibrosis-current clinical and therapeutic perspectives[J].Clin Oncol,2012,24(10):657-672.DOI:10.1016/j.clon.2012.04.001.
[2] Douhara A,Moriya K,Yoshiji H,et al. Reduction of endotoxin attenuates liver fibrosis through suppression of hepatic stellate cell activation and remission of intestinal permeability in a rat non-alcoholic steatohepatitis model[J].Mol Med Rep,2015,11(3):1693-1700.DOI:10.3892/mmr.2014.2995. [3] Dooley S,ten Dijke P.TGF-β in progression of liver disease[J].Cell Tissue Res,2012,347(1):245-256.DOI:10.1007/s00441-011-1246-y.
[4] Inagaki Y,Okazaki I.Emerging insights into Transforming growth factor beta Smad signal in hepatic fibrogenesis[J].Gut,2007,56(2):284-292.DOI:10.1136/gut.2005-088690.
[5] Li HY,Zhang QG,Chen JW,et al. The fibrotic role of phosphatidylinositol-3-kinase/Akt pathway in injured skeletal muscle after acute contusion[J].Int J Sports Med,2013,34(9):789-794.DOI:10.1055/s-0032-1333284. [6] 吴戈,肖蕾,艾尼瓦尔·艾木都拉,等.放射性肝纤维化的实验研究中TNF-α、NF-κb p65和TGF-β-1动态变化及表达意义[J].中华放射肿瘤学杂志,2014,23(5):390-391.DOI:10.3760/cma.j.issn.1004-4221.2014.05.005.
Wu G,Xiao L,Animaer·A,et al. The dynamic change and express meaning of TNF-α, NF-κb p65 and TGF-β 1 for the radioactive liver fibrosis in the experimental study[J].Chin J Radiat Oncol,2014,23(5):390-391.DOI:10.3760/cma.j.issn.1004-4221.2014.05.005.
[7] Francisco JS,Moraes HP,Dias EP.Evaluation of the image-pro plus 4.5 software for automatic counting of labeled nuclei by PCNA immunohistochemistry[J].Braz Oral Res,2004,18(2):100-104.DOI:10.1590/S1806-83242004000200002. [8] Wu CT,Chen WC,Lin PY,et al. Androgen deprivation modulates the inflammatory response induced by irradiation[J].BMC Cancer,2009,9:92.DOI:10.1186/1471-2407-9-92. [9] Heras-Sandoval D,Pérez-Rojas JM,Hernández-Damián J,et al. The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration[J].Cell Signal,2014,26(12):2694-2701.DOI:10.1016/j.cellsig.2014.08.019. [10] Qin J,Xie YY,Huang L,et al. Fluorofenidone inhibits nicotinamide adeninedinucleotide phosphate oxidase via PI3K/Akt pathway in the pathogenesis of renal interstitial fibrosis[J].Nephrology,2013,18(10):690-699.DOI:10.1111/nep.12128. [11] 王云莲,艾尼瓦尔·艾木都拉,肖蕾,等.血清转化生长因子β-1在大鼠放射性肝纤维化中的动态表达及其相关性研究[J].现代生物医学进展,2014,14(30):5829-5832.DOI:10.13241/j.cnki.pmb.2014.30.008. Wang YL,Aimudula A,Xiao L,et al. Study on dynamic changes and correlation of serum levels of transforming growth factor β 1 and radiation-induced hepatic fibrosis in rat[J].Progress Modern Biomed,2014,14(30):5829-5832.DOI:10.13241/j.cnki.pmb.2014.30.008. [12] Jiang F,Wang XX,Liu QQ,et al. Inhibition of TGF-β/SMAD3/NF-κB signaling by microRNA-491 is involved in arsenic trioxide-induced anti-angiogenesis in hepatocellular carcinoma cells[J].Toxicol Lett,2014,231(1):55-61.DOI:10.1016/j.toxlet.2014.08.024. [13] 徐丽红,田德安,郑勇.转化生长因子-β/Smad和磷脂酰肌醇3激酶/蛋白激酶B的信号串扰与肝纤维化[J].中华传染病杂志,2013,31(2):120-124.DOI:10.3760/cma.j.issn.1000-6680.2013.02.017. Xu LH,Tian DA,Zheng Y. Transforming growth factor-β/Smad and phosphatidyl inositol 3 kinase/protein kinase B signal crosstalk and liver fibrosis[J].Chin J Infect Dis,2013,31(2):120-124.DOI:10.3760/cma.j.issn.1000-6680.2013.02.017. [14] Du SS,Qiang M,Zeng ZC,et al. Radiation-induced liver fibrosis is mitigated by gene therapy inhibiting transforming growth factor-β signaling in the rat[J].Int J Radiat Oncol Biol Phys,2010,78(5):1513-1523.DOI:10.1016/j.ijrobp.2010.06.046. [15] Du R,Xia L,Ning X,et al. Hypoxia-induced Bmi1 promotes renal tubular epithelial cell-mesenchymal transition and renal fibrosis via PI3K/Akt signal[J].Mol Biol Cell,2014,25(17):2650-2659.DOI:10.1091/mbc. E14-01-0044.
2016, Vol. 25 
