亚麻木酚素通过调控TXNIP/NLRP3信号通路改善CIH小鼠心肌损伤  

Secoisolariciresinol diglucoside improves myocardial injury by regulating TXNIP/NLRP3 signaling pathway in CIH mice

作　　者：任静 郭亚净 刘寒 周健 吉恩生 REN Jing;GUO Ya-jing;LIU Han;ZHOU Jian;JI En-Sheng(Dept of Physiology, Basic Medical College, Hebei University of Chinese Medicine,Shijiazhuang 050020,China)

机构地区：[1]河北中医学院基础医学院生理教研室,低氧生理与病理生理实验室,河北石家庄050020

出　　处：《中国药理学通报》2020年第8期1094-1099,共6页Chinese Pharmacological Bulletin

基　　金：河北中医学院省属高校基本科研业务费专项基金(No YJZ2019005)。

摘　　要：目的研究亚麻木酚素(secoisolariciresinol diglucoside,SDG)对慢性间歇性低氧(chronic intermittent hypoxia,CIH)小鼠心肌损伤的作用及其机制。方法SDG灌胃处理CIH小鼠,HE染色观察各组小鼠心肌组织和检测血清中CK、LDH-L浓度,观察SDG对CIH小鼠心肌损伤的影响;TBA、NBT法检测MDA、SOD水平,观测SDG对CIH小鼠心肌氧化应激的影响;ELISA法检测各组小鼠血清中TNF-α、IL-6、IL-1β的水平,观察SDG对CIH小鼠炎症因子的影响;Western blot方法检测TXNIP、NLRP3、caspase-1、ASC、IL-18和IL-1β蛋白表达,观察SDG对CIH小鼠心肌TXNIP/NLRP3信号通路的影响。结果CIH处理后,小鼠心肌病理切片可见明显的心肌细胞排列紊乱,胞核坏死,细胞明显肿胀,胞间隙增大,严重颗粒、空泡样变性,同时还有炎症细胞浸润,心肌纤维断裂溶解、坏死的病理改变,血清中LDH-L、CK浓度明显升高(P<0.01),心肌组织中MDA含量明显升高(P<0.01),SOD含量明显降低(P<0.01),TXNIP、NLRP3、caspase-1、ASC、IL-18和IL-1β蛋白表达明显升高。亚麻木酚素治疗后,CIH小鼠心肌病理切片可见心肌细胞排列大致整齐,血清中LDH-L、CK浓度明显下降(P<0.05),心肌组织匀浆中MDA含量明显下降(P<0.05),SOD含量明显升高(P<0.01),TXNIP、NLRP3、caspase-1、ASC、IL-18和IL-1β蛋白表达明显降低。结论亚麻木酚素通过抗氧化、抗炎机制,调节TXNIP/NLRP3信号通路改善CIH诱发小鼠的心肌损伤。Aim To investigate the effect of secoisolariciresinol diglucoside(SDG)on myocardial injury in chronic intermittent hypoxia(CIH)miceandits mechanism.Methods Chronic intermittent hypoxic mice were given SDG by gavage.The effects of SDG on myocardial injury in CIH mice were observed by HE staining,and the concentrations of CK and LDH-L in serum in each group of miceweredetected.TBA and NBT methods were used to detect MDA and SOD levels to observe the effects of SDG on oxidative stress in myocardium of CIH mice.ELISA was used to detect the levels of TNF-α,IL-6 and IL-1βin the serum of mice in each group to observe the effect of SDG on inflammatory factors in CIH mice.Western blot was used to detect the TXNIP,NLRP3,caspase-1,ASC,IL-18 and IL-1βprotein expressions to observe the effect of SDG on the TXNIP/NLRP3 signaling pathway in myocardium of CIH mice.Results After CIH treatment,the pathological changes of myocardial cells in mice showed obvious disordered arrangement in cardiomyocytes,necrosis of the nucleus,obvious swelling of the cells,increased intercellular space,severe granular degeneration,vacuole degeneration,infiltration of inflammatory cells,and lysis of myocardial fibers.The concentrations of LDH-L and CK in serum of mice increased significantly(P<0.01).MDA levelin myocardial tissue increased significantly(P<0.01),whileSOD level decreased significantly(P<0.01).The expression of TXNIP,NLRP3,caspase-1,ASC,IL-18 and IL-1βprotein increased significantly.After treatment with SDG,the myocardial pathological sections of CIH mice showed that the myocardial cells were roughly arranged.The concentrations of LDH-L and CK in serum decreased significantly.MDA in myocardial tissue homogenate decreased significantly,and SOD increased significantly.TXNIP,NLRP3,caspase-1,ASC,IL-18 and IL-1βprotein expression were significantly reduced.Conclusion SDG improves CIH-induced myocardial injury by regulating the TXNIP/NLRP3 signaling pathway in mice.

关 键 词：亚麻木酚素 间歇性低氧 氧化应激 心肌 TXNIP NLRP3炎性小体 

分 类 号：R-332[医药卫生] R282.71