rhNRG-1β对放射性心脏损伤保护作用的探讨  

Protective Effects of Neuregulin-1β on Myocardial Injury by Radiation

作　　者：盖凯 毕迎惠[1] 郭成业[1] 陈玲[1] 刘阳[1] GAI Kai;BI Yinghui;GUO Chengye;CHEN Ling;LIU Yang(Department of Oncology, the Qingdao Municipal Hospital (group), Qingdao, Shandong, 266011, China)

机构地区：[1]青岛市市立医院(集团)西院区肿瘤一科

出　　处：《肿瘤药学》2019年第3期470-474,共5页Anti-Tumor Pharmacy

摘　　要：目的 观察重组人神经调节蛋白-1β(rhNRG-1β)对放射性心脏损伤是否有保护作用,并初步分析其作用机制。方法 18只雌性SD大鼠,体重200~250g。分为3组:单纯辐照组(n=6),单次心脏局部放疗20Gy;rhNRG-1β处理组(n=6),连续5天尾静脉注射rhNRG-1β10μg·kg-1·d-1,随后接受心脏局部放疗20Gy;Herceptin处理组(n=6),连续5天尾静脉注射Herceptin2mg·kg^-1·d^-1,随后接受心脏局部放疗20Gy。放疗后3h取心肌组织行γ-H2AX免疫荧光染色,观察心肌细胞损伤情况,Westernblot检测p53蛋白表达量。结果 与单纯辐照组相比,rhNRG-1β处理组的γ-H2AX免疫荧光染色平均光密度显著降低(P<0.05),Herceptin处理组则显著升高(P<0.05)。与单纯辐照组比较,rhNRG-1β处理组p53蛋白表达明显下调(P<0.05),Herceptin处理组则明显上调(P<0.05)。结论 Herceptin可加重心肌组织的放射性损伤,而rhNRG-1β能够减轻心肌组织的放射性损伤。rhNRG-1β保护心肌组织的机制可能是通过激活心脏的EGFR通路发挥作用。Objective To investigate the protection effects of rhNRG-1β on radiation-induced myocardial damage, and preliminarily analyze its mechanism. Methods 18 female SD rats weighing 200 to 250 g were randomly divided into 3 groups: pure irradiation group (n=6) was given an localized heart irradiation with a single dose of 20 Gy;rhNRG-1β treatment group (n=6) was given an injection of rhNRG- 1β at 10 μg· kg^-1·d^-1 via tail vein for 5 days just before the irradiation as that of the pure irradiation group;Herceptin treatment group (n=6) was given an injection of Herceptin at 2mg· kg-1·d-1 via tail vein for 5 days just before the irradiation as that of the pure irradiation group. Three hours after irradiation,γ-H2AX immunofluorescence staining was performed to observe the occurrence and repair of DNA doublestrand break (DSB). Western blot was applied to detect the concentration of p53 protein. Results Compared with pure irradiation group, the average optical density of γ-H2AX immunofluorescence staining decreased significantly in rhNRG-1β treatment group (P<0.05), but increased significantly in Herceptin treatment group (P<0.05). Moreover, compared with pure irradiation group, the concentration of p53 protein decreased significantly in rhNRG-1β treatment group (P<0.05), but increased significantly in Herceptin treatment group (P<0.05). Conclusion rhNRG-1β could reduce the radiation injury to myocardial tissue, and Herceptin has the opposite effect. rhNRG-1β may play the protective role through activating EGFR pathway in the heart.

关 键 词：放射性心脏损伤 EGFR通路 重组人神经调节蛋白1β HERCEPTIN 

分 类 号：R730.6[医药卫生—肿瘤]