辛伐他汀减轻放射性肺损伤的初步研究

Simvastatin reduces radiation-induced lung injury:A preliminary study

目的:探讨辛伐他汀对C57BL/6小鼠放射性肺损伤的防护作用及其可能作用机制。方法:将80只C57BL/6小鼠随机分为空白组(不照射,予生理盐水0.3mL/只)、单药组(不照射,予辛伐他丁原液)、单放组(胸部照射)、联合组(胸部照射+予辛伐他丁原液),每组20只小鼠。采用6MvX射线大剂量照射小鼠全肺ARILI模型,总剂量为15Gy。照射后4h,单药组和联合组小鼠每天辛伐他汀10mg·kg^(-1)灌胃,单放组和空白组每天饲以0.9%氯化钠溶液,连续灌胃30d。在照射后8周、16周、24周取小鼠肺组织进行HE染色和Masson染色观察组织病理学变化;采用紫外分光光度计检测肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活力和羟脯氨酸(Hyp)含量。ELISA法检测小鼠血清转化生长因子β_(1)(TGF-β_(1))、肿瘤坏死因子α(TNF-α)含量。结果:联合组小鼠肺组织损伤和肺纤维化较单放组小鼠明显减轻,其血清TGF-β_(1)和TNF-α表达水平略高于空白组,与单放组相比明显降低,差异有统计学意义(P<0.05);联合组小鼠肺组织MDA含量和Hyp含量略高于空白组,与单放组相比明显降低,差异有统计学意义(P<0.05);联合组小鼠肺组织SOD活力高于单放组,但低于空白组和单药组,差异有统计学意义(P<0.05);空白组小鼠各项检测指标与单药组相比,差异均无统计学意义(P均>0.05)。结论:辛伐他汀对C57BL/6小鼠肺组织具有放射保护作用,其机制可能与减轻组织氧化应激、下调炎性因子等有关。

Objective:To explore the possible mechanism of the prevention effect of simvastatin on radiation induced pul⁃monary injury using a C57BL/6 mouse model.Methods:Eighty C57BL/6 mice were randomly divided into four groups:blank control group(group A),simvastatin alone(group B),irradiation alone(group C),and irradiation plus simvas⁃tatin group(group D),20 mice in each group.The models of RILl in C57BL/6 mice in groups C and D were established by whoIe 4MV X-rays irradiation with a singIe dose of 15 Gy.Four hours after radiation,the mice in group B and group D were administered daily via gavage with simvastatin(10 mg·kg^(-1))for 30 d,while the same volume of normal saline solu⁃tion was given daily in the group A and group C.After 8 weeks,16 weeks and 24 weeks,the pathological changes of the lung srained with HE/Masson were observed with a light microscope.The transforming growth factor-β_(1)(TGF-β_(1))and tumor necrosis factor-a(TNF-α)in serum were examined by enzyme-linked immunosorbent assay.The activities of malondial⁃dehvde(MDA)and superoxide dismutase(SOD)and the content of hydroxyproline in lung tissues were examined by cor⁃responding kits.Results:Compared with group C,there was an obvious amelioration in pathological injury of lung tissue in group D.The activities of lung tissue MDA,the serum content of hydroxide free radical and the serum levels of TGF-β_(1) and TNF-αin group D were significantly lower than those in group C(P<0.05),while slightly higher than those in group A(P<0.05).The activity of SOD was significantly higher in group D than that in group C,while lower than those in group A and group B(P<0.05).There were no statistically significant differences in these indicators between group A and group B(P>0.05).Conclusion:Simvastatin could protect C57BL/6 mice lung from radiation injury probably by alleviationg oxidative.