竹节参总皂苷通过调节AMPKSirt1NF―κB通路抑制衰老大鼠心肌细胞凋亡作用研究.docVIP

竹节参总皂苷通过调节AMPKSirt1NF―κB通路抑制衰老大鼠心肌细胞凋亡作用研究 　　[摘要] 研究竹?参总皂苷（saponins extracted from Panax japonicus，SPJ）对自然衰老大鼠心肌细胞凋亡的调节作用及其作用机制。将SD雄性大鼠随机分为青年对照组、自然衰老组、SPJ低剂量组、SPJ高剂量组，每组10只。自然衰老组、SPJ低、高剂量组从18月龄开始分别灌胃给予生理盐水、SPJ 10，60 mg?kg-1?d-1，每周灌胃6 d，持续6个月至24月龄处理动物。HE染色观察各组大鼠心肌形态；Tunel法检测心肌细胞凋亡；Western blot检测各组大鼠心肌组织中Bcl-2，Bax，IL-1β，TNF-α，AMPK，p-AMPK，Sirt1，Ac-NF-κB p65蛋白表达。SPJ能有效改善自然衰老大鼠心肌纤维的排列紊乱，减少炎性细胞浸润，抑制心肌细胞凋亡。同时，SPJ能明显抑制自然衰老过程中心脏组织Bax，IL-1β，TNF-α，Ac-NF-κB p65的表达，促进Bcl-2，Bcl-2/Bax，p-AMPK/AMPK，Sirt1蛋白表达。SPJ可有效抑制自然衰老大鼠心肌细胞凋亡，其作用机制可能与调节AMPK/Sirt1/NF-κB通路介导的炎症反应有关。 　　[关键词] 竹节参总皂苷； 自然衰老大鼠； 心肌细胞凋亡； 炎症反应； AMPK/Sirt1/NF-κB信号通路 　　[Abstract] To investigate the effects of saponins extracted from Panax japonicus（SPJ） on cardiomyocyte apoptosis in natural aging rats and explore its underlying mechanisms. SD male rats were randomly divided into four groups： young control group， natural aging group， SPJ low dose group and SPJ high dose group， with 10 rats in each group. The rats in natural aging group， SPJ low and high dose groups were respectively treated with normal saline， SPJ 10 and 60 mg?kg-1?d-1 from the beginning of 18 month-old， 6 days per week for 6 months till 24 month-old. Then the animals were sacrificed. Their myocardial morphology changes were observed by using haematoxylin-eoin（HE） staining； cardiomyocyte apoptosis was tested by using Tunel assays； and the protein expression levels of Bcl-2， Bax， IL-1β， TNF-α， AMPK， p-AMPK， Sirt1， and Ac-NF-κB p65 in myocardial tissues of rats were detected by Western blot. The results showed that SPJ could effectively improve the arrangement disorder of myocardial fibers， reduce the infiltration of inflammatory cells and inhibit cardiomyocyte apoptosis in natural aging rats. At the same time， SPJ could significantly inhibit the protein expression of Bax， IL-1β， TNF-α and Ac-NF-κB p65， and increase the expression of Bcl-2， Bcl-2/Bax， p-AMPK/AMPK and Sirt1 in the heart tissues of natural aging rats. SPJ can effectively inhibit cardiomyocyte