血清转化生长因子beta-1 在大鼠放射性肝纤维化中的动态表达 及其相关性研

目的:肝癌的放射治疗可导致放射性肝损伤(RILD)、甚至肝纤维化及肝硬化等并发症的发生,因此寻找较佳的血清标记物对放射性肝纤维化的无创诊断及监测具有重要意义。本文通过建立放射性肝纤维化大鼠模型,检测血清转化生长因子β1(TGF-β1)的动态表达,从而探讨其与放射性肝纤维化严重程度的相关性及其作为血清标记物的诊断价值。方法:雄性SD大鼠40只,随机分为模型组(30只)和对照组(10只)。除对照组外,模型组大鼠右半肝均接受单次6MV X线25Gy照射,于照射2月、4月、6月后,随机抽取10只,酶联免疫吸附法(ELISA)检测血清TGF-β1的表达,同时将大鼠肝组织进行HE染色,观察肝组织病理变化及大鼠肝纤维化程度,将后者与血清TGF-β1值进行相关性分析。结果:在照射第2月、4月、6月后,模型组大鼠血清TGF-β1值(分别为551.03±69.00 ng/L、645.31±109.29 ng/L、737.89±118.11 ng/L)逐渐升高,均明显高于对照组(451.71±51.12 ng/L,P<0.05)。通过相关性分析表明,大鼠血清TGF-β1值与肝纤维化程度正相关(r=0.82,P<0.01)。结论:在放射性肝纤维化发生发展中,TGF-β1随着肝纤维化严重程度增加,其表达亦升高。本研究为放射性肝纤维化严重程度的监测提供了一种新的无创、操作简单的手段,为后续TGF-β1作为血清标记物应用于放射性肝纤维化的临床研究奠定了理论基础。

Study on Dynamic Changes and Correlation of SerumLevels of Transforming Growth Factor beta1 and Radiation-induced Hepatic Fibrosis in Rat

Objective:Radiation therapy of liver carcinoma may lead to the complication of radiation- induced liver disease (RILD), hepatic fibrosis, even hepatic cirrhosis. So it is of great significance to look for better serum markers for noninvasively diagnosing and monitoring radiation-induced hepatic fibrosis. In this study, we established the rats model of radiation-induced hepatic fibrosis, detected the dynamic changes of serumlevels of transforming growth factor beta 1(TGF-beta1), explored the correlation of TGF-beta1 and the severity of radiation-induced hepatic fibrosis, and discovered the diagnosis value of TGF-beta1.Methods:Forty healthy male Sprague-Dawley rats were randomly divided into model group (30 rats) and control group (10 rats). The right-half of rat liver in model group was irradiated with a single dose of 25 Gy to establish radiation-induced hepatic fibrosis model. Liver tissues from the irradiated liver, and blood sample were collected at different time points(2 months, 4 months, 6 months) after irradiation. Expression of TGF-beta1 by enzyme-linked immunosorbent assay (ELISA) was performed. Pathomorphological change in the liver was observed with hematoxylineosin staining by optical microscope.Results:The expression of serum TGF-beta1 of model group at different time points 2 months, (551.03± 69.00) ng/L; 4 months, (645.31± 109.29) ng/L; 6 months, (737.89± 118.11) ng/L] was significantly higher than that of the control group (451.71± 51.12 ng/L, P<0.05). There were distinctly positive correlation between the serum of TGF-beta1 value and severity of hepatic fibrosis (r=0.82, P<0.01).Conclusion:In the development of radiation- induced fibrosis, TGF-beta1 rises with the severity of hepatic fibrosis. We provide a new noninvasive and convenient means for monitoring the severity of hepatic fibrosis, and lay a theoretical foundation for subsequent TGF-beta1 as a serummarker applied to clinical research of radiation-induced hepatic fibrosis.