摘要
目的探讨意大利牛舌草总黄酮及四种化学成分对心肌细胞缺氧/复氧损伤(hypoxia-reoxygenation,H/R)的保护作用及作用机制。方法分离并培养原代乳鼠心肌细胞,随机分组,建立H/R模型,给药后测定相关指标。结果与模型组相比,总黄酮及四种化学成分均能增加心肌细胞缺氧/复氧损伤后的存活率(P<0.01),降低LDH漏出量(P<0.01),减少细胞内MDA的含量(P<0.01),且SOD活力显著性提高(P<0.01),可显著降低心肌细胞早期凋亡指数,提高线粒体膜电位(P<0.01)。给药组NF-κB信号通路关键蛋白的激活受到抑制,Bax/Bcl-2比例明显降低(P<0.01),Beclin-1蛋白表达量明显降低而p62表达上调(P<0.01),焦亡相关蛋白NLRP3、IL-1β以及GSDMD明显降低(P<0.01)。结论意大利牛舌草总黄酮及四种化学成分可通过抑制NF-κB信号通路的激活及心肌细胞的过度自噬,缓解细胞焦亡,减少心肌细胞凋亡,减轻H/R对心肌细胞造成的损伤。
Aim To observe the protective effects of total flavonoids from Anchusa italica Retz.and four compounds on hypoxia/reoxygenation(H/R)injury in myocardial cells and to explore the mechanisms.Methods Primary neonatal rat cardiomyocytes were isolated,cultured and were randomly divided into different groups.The H/R model of cultured neonatal rat cardiomyocytes was developed.The related indexes were determined after administration.Results Compared with model group,the total flavonoids and the four compounds could increase the survival rate of H/R cardiomyocytes(P<0.01),reduce the leakage of LDH(P<0.01),reduce the content of MDA(P<0.01),significantly increase the activity of SOD(P<0.01),significantly decrease the early apoptosis index and increase the mitochondrial membrane potential(P<0.01).The activation of key proteins in NF-κB signaling pathway was inhibited,the proportion of Bax/Bcl-2,beclin-1 and p62 significantly decreased(P<0.01),and the expression of apoptosis related proteins NLRP3,IL-1βand GSDMD significantly decreased(P<0.01).Conclusions The total flavonoids and four compounds can alleviate the damage of H/R on cardiomyocytes.The mechanism is related to the inhibition of the activation of NF-κB signaling pathway and the excessive autophagy of cardiomyocytes,alleviation of the scorch death of cardiomyocytes,and reduction of the apoptosis of cardiomyocytes.
作者
滕亮
李蒙华
马桂芝
TENG Liang;LI Meng-hua;MA Gui-zhi(Pharmacy Dept,the First Affiliated Hospital of Xinjiang Medical University,Urumuqi 830054,China;Dept of Pharmacy,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Dept of Pharmaceutical Analysis,College of Pharmacy,Xinjiang Medical University,Urumuqi 830011,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2021年第3期409-416,共8页
Chinese Pharmacological Bulletin
基金
新疆维吾尔自治区自然科学基金项目(No 2017D01C19)。
关键词
意大利牛舌草总黄酮
化学成分
心肌细胞
缺氧/复氧损伤
机制
total flavonoids from Anchusa italica Retz.
chemical compounds
cardiomyocytes
hypoxia/reoxygenation injury
mechanism
