首页|人参皂苷Rb1调控线粒体自噬对脓毒症血管内皮的保护作用及其机制研究

人参皂苷Rb1调控线粒体自噬对脓毒症血管内皮的保护作用及其机制研究

The protective effects and mechanisms of ginsenoside Rb1 on vascular endothelium of sepsis by regulating mitophagy

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目的 研究人参皂苷Rb1通过磷脂酰肌醇-3激酶/蛋白激酶B/糖原合成激酶3β(PI3K/AKT/GSK3β)信号通路调控线粒体自噬对脓毒症血管内皮的保护作用及机制.方法 健康SPF级雄性昆明小鼠30只随机分为5组:假手术组(Sham组)、脓毒症组(CLP组)、人参皂苷Rb1+脓毒症组(人参皂苷Rb1组)、PI3K抑制剂LY294002+人参皂苷Rb1+脓毒症组(LY294002组)和线粒体自噬抑制剂Mdivi-1+人参皂苷Rb1+脓毒症组(Mdivi-1组),每组6只.采用盲肠结扎穿孔术(CLP)复制脓毒症小鼠模型,每组给予相应药物处理.术后观察小鼠一般情况,24 h后取主动脉组织样本,通过苏木素—伊红(HE)染色观察主动脉组织病理学改变,免疫组织化学法检测vWF、p-AKT、p-GSK3β及线粒体自噬相关蛋白Parkin的水平.结果 Sham组及人参皂苷Rb1组小鼠一般情况及腹腔感染情况较轻,主动脉组织内膜结构完整,细胞排列较整齐,形态分布规则;CLP组和抑制剂组均可见不同程度的内膜损伤突起,中膜增生且排列紊乱,管壁厚薄不一.免疫组化结果显示,与Sham组比较,CLP组小鼠主动脉vWF、Parkin表达升高(P<0.05),p-AKT、p-GSK3 β表达降低(P<0.05).与CLP组比较,人参皂苷Rb1组vWF表达明显降低(P<0.05),p-AKT、p-GSK3β 及 Parkin 表达升高(P<0.05).与人参皂苷 Rb1 组比较,LY294002 组 p-AKT、p-GSK3β 及Parkin表达降低,vWF升高(P<0.05),Mdivi-1组p-AKT及p-GSK3β表达差异无统计学意义(P>0.05),Parkin表达明显降低,vWF 升高(P<0.05).与 LY294002 组比较,Mdivi-1 组 p-AKT、p-GSK3β 表达明显升高(P<0.05),Parkin表达降低(P<0.05).结论 人参皂苷Rb1通过激活PI3K/AKT/GSK3β信号通路促进血管内皮细胞线粒体自噬,进而对脓毒症血管内皮起保护作用.
Objective To study the protective effect and mechanism of ginsenoside Rb1 on vascular endothelium of sepsis by regulating mitophagy through phosphatidylinositol-3 kinase/protein kinase B/glycogen synthase kinase 3β(PI3K/AKT/GSK3β)signaling pathway.Methods Healthy male Kunming mice were randomly divided into 5 groups:Sham operation group(Sham group),sepsis group(CLP group),ginsenoside Rb1+sepsis group(ginsenoside Rbl group),PI3K inhibitor LY294002+ginsenoside Rb1+sepsis group(LY294002 group)and mitophagy inhibitor Mdivi-1+ginsenoside Rb1+sepsis group(Mdivi-1 group).The sepsis mouse model was replicated by cecal ligation and puncture(CLP).Each group was treated with corresponding drugs.The general condition of mice was observed after operation.After 24 hours,aortic tissue samples were taken to observed the pathological changes by Hematoxylin-eosin(HE)staining and detected the expression levels of vWF,p-AKT,p-GSK3β and Parkin by immunohistochemistry.Results The general condition and ab-dominal infection of mice in the Sham group and the ginsenoside Rb1 group were mild,the intima structure of the aortic tis-sue was complete,the cells were arranged neatly,and the shape distribution was regular.In the CLP group and the inhibitor group,there were different degrees of intimal damage hyperplasia and disordered arrangement of the media,and different thickness of the wall.Immunohistochemical results showed that compared with the Sham group,the expression of vWF and Parkin in the CLP group was increased(P<0.05),and the expression of p-AKT and p-GSK3β was decreased(P<0.05).Compared with the CLP group,the expression of vWF in the ginsenoside Rb1 group was significantly decreased(P<0.05),and the expression of p-AKT,p-GSK3β and Parkin was increased(P<0.05).Compared with ginsenoside Rb1 group,the ex-pression of p-AKT,p-GSK3β and Parkin were decreased in LY294002 group(P<0.05),and the expressions of p-AKT and p-GSK3β were not significantly different in Mdivi-1 group,but the expression of Parkin was significantly decreased(P<0.05).Compared with LY294002 group,the expression of p-AKT and p-GSK3β was significantly increased(P<0.05),and the expres-sion of Parkin was decreased in Mdivi-1 group(P<0.05).Conclusion Ginsenoside Rb1 promotes mitophagy by activating PI3K/AKT/GSK3β signaling pathway,which has a protective effect on vascular endothelium in patients with sepsis.

SepsisGinsenoside Rb1Vascular endotheliumMitochondrial autophagyPI3K/AKT/GSK3β signa-ling pathwayMechanism

卢彩云、刘畅、黄敏、张洪泉、陶星宇、贾宝辉

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453000 河南新乡,新乡医学院

450000 郑州,郑州大学附属郑州中心医院急诊科

330000 南昌,南昌市第一医院老年医学科

330000 南昌,南昌大学

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脓毒症 人参皂苷Rb1 血管内皮 线粒体自噬 PI3 K/AKT/GSK3 β通路 作用机制 小鼠

河南省重点研发与推广专项(科技攻关)项目江西省青年科学基金资助项目江西省中医药管理局科技计划课题

2121023107242020BABL2160022022B325

2024

疑难病杂志
中国医师协会

疑难病杂志

CSTPCD
影响因子:1.171
ISSN:1671-6450
年,卷(期):2024.23(10)
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