大鼠急性放射性肝损伤及其保护的实验研究

Study on Mechanisms of Radiation-induced Hepatic Injury and Its Protection

目的:探讨活性氧自由基(ROS)、一氧化氮(NO)和TGF-β1在大鼠急性放射性肝损伤中的机制及细胞保护剂安福定对大鼠急性放射性肝损伤的保护作用。方法:健康雄性SD大鼠48只,随机分成正常对照组(C组)、安福定组(A组)、单纯照射组(X组)3组各16例。正常对照组不予照射。其余两组给予一次性全肝照射,照射剂量20Gy。安福定组于照射前30 min腹腔内注射安福定200mg/kg;单纯照射组则照射前腹腔注射等容量的生理盐水。结果:照射后第4、8、14天的血ALT、AST、肝组织光镜未出现明显变化。电镜下明显的超微结构改变。单纯放射组大鼠血浆ROS活性明显高于正常对照组(P<0.05)。安福定组血浆MDA含量显著低于正常对照组,而SOD活性则高于正常对照组。单纯放射组大鼠血浆NO含量明显高于正常对照组和安福定组P<0.05)。照射后第14天单纯放射组大鼠血浆TGF-β1含量明显高于正常对照组和安福定组(P<0.05)。结论:ROS、NO和TGF-β1都参与了急性放射性肝损伤。NO和TGF-β1则分别作为炎症介质和炎性细胞因子在损伤的进程中起关键作用。安福定对放射性肝损伤有保护作用。测定血MDA含量及SOD活性、NO和TGF-β1比血AL、AST更早提示放射性肝损伤。

Objective： To observe the effects of oxygen free radical（ROS） ,nitric oxide（NO） and TGF-β1 on the acute radiation-induced hepatic injury of rats. The protective effect of amifostine against radiation was also discussed. Methods： Forty-eight SD rats were divided into normal group, radiated group, and amifostine-pretreated group. The models were made by a single radiation of 20Gy on whole liver except the normal group. Amifostine was given intraperitoneally （200mg/kg） 30 minutes before irradiation to amifostine group. The levels of plasma ROS,NO, TGF-β1 in rats were measured on the 4th,8th and 14th day after radiation. Animals were euthanized 14 days after irradiation, and the hepatic tissues were observed under microscope and electronficroscope. The plasma concentrations of AST,ALT of rats were also measured. Results： The hepatic cells showed no difference among three group under the mi- croscope, but some changes were observed by the transmission electromicroseope. No significant difference of AST,ALT were observed among three groups. The concentrations of ROS significantly increased in radiated group （P 〈 0. 05 ）. In group Amifostine ,the activity of SOD increased while the level of MDA decreased compared with the normal group（ P 〈 0. 05）. The concentrations of NO were significantly higher in radiated group（ P 〈 0. 05 ）. On the 14th day after radiation the concentrations of TGF-β1 increased significantly in radiated group （P 〈0. 05）. Conclusion： ROS,NO and TGF-β1 play an important part in the acute radiation-induced hepatic injury of rats. Amifostine has a marked protective effect to hepatic injury. The plasma concentration changes of ROS,NO,TGF-β1 are much earlier than AST,ALT of rats with radiation-induced hepatic injury.