红景天苷对糖尿病大鼠心肌炎症因子和Hippo信号通路相关蛋白的影响
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R 587.23

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上海市虹口区"国医强优"三年行动计划(HGY-KY-2018-04).


Effects of salidroside on myocardial inflammatory cytokines and Hippo signaling pathway-related proteins in diabetes mellitus rats
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    摘要:

    目的 探讨红景天苷(SAL)对糖尿病(DM)大鼠心肌炎症因子和Hippo信号通路相关蛋白的影响。方法 将4周龄雄性SD大鼠随机分为3组,空白对照组、DM模型组[链脲佐菌素(STZ)组]、SAL干预组(SAL组),每组5只。大鼠DM模型的建立使用STZ诱导方案,SAL作为DM模型大鼠的干预措施。用H-E染色和Masson染色观察大鼠心肌病理学改变,TUNEL染色观察心肌细胞凋亡情况。用ELISA法检测心肌组织和外周血中TNF-α、IL-1β和IL-6表达水平,用蛋白质印迹法分析Hippo信号通路相关蛋白表达水平,用RT-PCR法检测Yes相关蛋白(Yap) mRNA含量。结果 与空白对照组相比,STZ组大鼠心肌细胞排列紊乱,纤维化增加,心肌细胞凋亡率增加(P<0.01);TNF-α、IL-1β和IL-6表达升高(P均<0.01);Hippo信号通路相关蛋白哺乳动物Ste20样激酶1/2(Mst1/2)、大肿瘤抑制基因1/2(Lats1/2)和Yap表达升高(P<0.05,P<0.01),磷酸化(p)-Mst1/2、p-Lats1/2和p-Yap表达降低(P均<0.01),Yap/p-Yap比值升高(P<0.01),Yap mRNA表达水平升高(P<0.01)。SAL干预后心肌细胞纤维化和凋亡率降低(P<0.01),TNF-α和IL-6表达水平下降(P<0.05,P<0.01),Yap/p-Yap比值降低(P<0.01),Yap mRNA表达水平降低(P<0.01)。结论 SAL能改善DM大鼠心肌细胞功能,其机制可能与抑制炎症反应、减少细胞凋亡及调节Yap/p-Yap比值有关。

    Abstract:

    Objective To investigate the effects of salidroside (SAL) on myocardial inflammatory cytokines and Hippo signaling pathway-related proteins in diabetes mellitus (DM) rats.Methods Four weeks old male SD rats were randomly divided into 3 groups:blank control group,DM model group (streptozotocin[STZ]group),and SAL intervention group (SAL group),with 5 rats in each group.Rat DM model was induced by intraperitoneal injection of STZ,and SAL was used to treat DM rats.Pathological changes of rat myocardium were observed by hematoxylin-eosin staining and Masson staining,and apoptosis of cardiomyocytes was analyzed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining.The expression of tumor necrosis factor α(TNF-α),interleukin (IL)-1β and IL-6 in myocardial tissues and peripheral blood was evaluated by enzyme-linked immunosorbent assay (ELISA).The expression of Hippo signaling pathway-related proteins was detected by Western blotting,and Yes-associated protein (Yap) mRNA was detected by real-time polymerase chain reaction.Results Compared with the blank control group,the arrangement of cardiomyocytes in the STZ group was disordered,myocardial fibrosis and apoptosis rate (P<0.01) were increased,the expression levels of TNF-α,IL-1β and IL-6 were significantly increased (all P<0.01),the expression of Hippo signaling pathway-related proteins mammalian sterile-20 like protein kinase 1/2(Mst1/2),large tumor suppressor 1/2(Lats1/2) and Yap was increased (P<0.05,P<0.01),the expression of phosphorylated (p)-Mst1/2,p-Lats1/2 and p-Yap was decreased (all P<0.01),Yap/p-Yap ratio was increased (P<0.01),and the expression level of Yap mRNA was also increased (P<0.01).After SAL intervention,myocardial fibrosis and the rate of apoptosis (P<0.01) were decreased,the expression levels of TNF-α and IL-6 were decreased (P<0.05,P<0.01),and the ratio of Yap/p-Yap and the expression of Yap mRNA were decreased (both P<0.01).Conclusion SAL can improve the cardiomyocyte function in DM rats,and the mechanism may be associated with inhibiting inflammatory reaction,reducing cardiomyocytes apoptosis and regulating Yap/p-Yap ratio.

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  • 收稿日期:2021-02-07
  • 最后修改日期:2021-04-26
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  • 在线发布日期: 2022-09-27
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