Hu Zongtao, Qin Feng, Gao Shile, Zhen Yilan, Huang Dake, Dong Liuyi
Center of Cancer, The 105th Hospital of Chinese People's Liberation Army, Clinical College of Anhui Medical UniversityHefei 230031, People's Republic of China.
Hefei Cancer Hospital, Chinese Academy of SciencesHefei 230031, People's Republic of China.
Am J Transl Res. 2018 Mar 15;10(3):1012-1021. eCollection 2018.
This study aimed to investigate the protective effects of paeoniflorin (PAE) on radiation-induced hepatic fibrosis in a rat model.
Fifty healthy male Sprague-Dawley rats were randomly assigned to normal control group, hepatic fibrosis group, and PAE treatment groups. X-ray exposure was employed to establish radiation-induced hepatic fibrosis model. PAE was administered once daily, and rats were sacrificed at week 26 after irradiation. The liver histopathology was evaluated under a light microscope after HE staining and Masson staining. Meanwhile, the protein expression of transforming growth factor-beta 1 (TGF-β1), Smad3/4 and Smad7 was detected by immunohistochemistry.
Radiation-induced liver damage and collagen deposition were observed in the model group as compared to normal control group, but PAE treatment significantly attenuated the liver injury and reduce collagen deposition (P<0.05 or 0.01). The hepatic hydroxyproline content and serum levels of TGF-β1, hyaluronic acid, ro-collagen type III and laminin markedly increased in model group as compared to control group (P<0.01), but they decreased dramatically after PAE treatment. The expression of TGF-β1, Smad3/4 and Smad7 in the liver increased significantly in model group as compared to control group (P<0.01), and PAE could down-regulate the expression of Smad3/4 and up-regulate Smad7 expression (P<0.05 or 0.01). The activities of serum amino-transferase and aspartate aminotransferase were significantly higher in hepatic fibrosis group than in normal control group, but PAE treatment markedly reduced them (P<0.05).
PAE can inhibit the radiation induced hepatic fibrosis via regulating TGF-β1/Smads signaling pathway.
本研究旨在探讨芍药苷（PAE）对大鼠辐射诱导性肝纤维化的保护作用。
将50只健康雄性Sprague-Dawley大鼠随机分为正常对照组、肝纤维化组和PAE治疗组。采用X射线照射建立辐射诱导性肝纤维化模型。PAE每日给药1次，照射后26周处死大鼠。HE染色和Masson染色后，在光学显微镜下评估肝脏组织病理学。同时，通过免疫组织化学检测转化生长因子-β1（TGF-β1）、Smad3/4和Smad7的蛋白表达。
与正常对照组相比，模型组观察到辐射诱导的肝损伤和胶原沉积，但PAE治疗显著减轻了肝损伤并减少了胶原沉积（P<0.05或0.01）。与对照组相比，模型组肝羟脯氨酸含量以及TGF-β1、透明质酸、III型前胶原和层粘连蛋白的血清水平显著升高（P<0.01），但PAE治疗后它们显著降低。与对照组相比，模型组肝脏中TGF-β1、Smad3/4和Smad7的表达显著增加（P<0.01），PAE可下调Smad3/4的表达并上调Smad7的表达（P<0.05或0.01）。肝纤维化组血清氨基转移酶和天冬氨酸氨基转移酶的活性显著高于正常对照组，但PAE治疗显著降低了它们（P<0.05）。
PAE可通过调节TGF-β1/Smads信号通路抑制辐射诱导的肝纤维化。
