白藜芦醇上调SIRT1表达介导对放射性心肌损伤的保护作用  

Resveratrol up regulates the expression of SIRT1 and mediates protective effect on radiation-induced myocardial injury

作　　者：徐祎琳 陈燕欣 蔡旖旎 徐芃 曾治民[1] 黄龙[1] 刘安文[1] Xu Yilin;Chen Yanxin;Cai Yini;Xu Peng;Zeng Zhimin;Huang Long;Liu Anwen(Department of Oncology,the Second Affiliated Hospital of Nanchang University,Jiangxi Key Laboratory of Clinical Translational Cancer Research,Radiation Induced Heart Damage Institute of Nanchang University,Nanchang 330006,China)

机构地区：[1]南昌大学第二附属医院肿瘤科江西省肿瘤临床转化重点实验室南昌大学放射性心脏损伤研究所,南昌330006

出　　处：《中华放射肿瘤学杂志》2023年第5期457-463,共7页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金(82060577)。

摘　　要：目的研究白藜芦醇对小鼠放射性心肌损伤的影响。方法将80只C57BL/6小鼠随机分为对照组、白藜芦醇(Res)组、放射(RT)组以及放射+白藜芦醇(RT+Res)组。RT组小鼠予心脏放射,Res组小鼠予白藜芦醇灌胃3个月。在小鼠心脏放射后3个月使用心脏超声评估心功能,收集小鼠心脏进行HE染色、免疫荧光、TUNEL染色以及Masson染色、蛋白质印迹法等评估心肌组织沉默信息调节因子1(SIRT1)的表达、氧化应激水平、炎症反应、凋亡以及纤维化程度。实验数据用x¯±s描述,连续变量采用t检验进行统计分析。结果放射3个月后,相较于对照组,RT组小鼠心功能射血分数(EF)和心室短轴缩短率(FS)下降,心肌细胞变性、排列紊乱,活性氧(ROS)、炎症水平[白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α]、心肌凋亡(TUNEL阳性细胞率)和纤维化增加。而RT+Res组小鼠心功能改善,SIRT1表达增加,氧化应激、炎症水平、心肌凋亡和纤维化减少。结论白藜芦醇可降低放射性心肌损伤小鼠的心肌组织氧化应激、炎细胞浸润、心肌细胞凋亡和纤维化,改善心脏结构异常和心功能不全,在放射性心肌损伤中发挥保护作用,这种保护作用可由其上调SIRT1表达所介导。Objective To evaluate the effect of resveratrol on radiation-induced myocardial injury in mice.Methods A total of 80 C57BL/6 mice were randomly divided into the control group,resveratrol(Res)group,radiation(RT)group and radiation+resveratrol(RT+Res)group.In the RT group,mice were given with heart radiation and mice in the Res group were given with resveratrol by gavage for 3 months.Cardiac ultrasound was used to evaluate cardiac function at 3 months after cardiac radiation.The hearts of mice were collected for HE staining,immunofluorescence,TUNEL staining,Masson staining and Western blot to evaluate the expression of silent information regulator 1(SIRT1),the level of oxidative stress,inflammatory response,apoptosis and the degree of fibrosis in myocardial tissues.Experimental data were expressed as Mean±SD.Continous data were statistically analyzed by t-test.Results After 3 months of irradiation,compared with the control group,the ejection fraction(EF)and fractional shortening(FS)of cardiac function were decreased,and myocardial degeneration and disorder,reactive oxygen species(ROS)and inflammatory levels(interleukin-1β,interleukin-6,tumor necrosis factor-α),myocardial apoptosis(TUNEL positive cell rate)and fibrosis were increased in the RT group.In the RT+Res group,the cardiac function was improved,the expression of SIRT1 was increased,and the levels of oxidative stress,inflammation,myocardial apoptosis and fibrosis were decreased.Conclusions Resveratrol can reduce oxidative stress,inflammatory infiltration,apoptosis and fibrosis of myocardium in mice with radiation-induced myocardial injury,thereby improving cardiac structural abnormalities and cardiac dysfunction.This protective effect can be mediated by upregulation of SIRT1 expression.

关 键 词：放射性心肌损伤 白藜芦醇 沉默信息调节因子1 氧化应激 炎症 凋亡 纤维化 

分 类 号：R285.5[医药卫生—中药学]