| 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。 |
| 关键词: 糖尿病 糖尿病心肌病 红景天苷 Hippo信号通路 炎症 |
| DOI：10.16781/j.CN31-2187/R.20210130 |
| 投稿时间：2021-02-07修订日期：2021-04-26 |
| 基金项目:上海市虹口区"国医强优"三年行动计划(HGY-KY-2018-04). |
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| Effects of salidroside on myocardial inflammatory cytokines and Hippo signaling pathway-related proteins in diabetes mellitus rats |
| GU Yan-ni1，2，3,WANG Song2,XIA Kun-jie2,XIE Chun-yi1* |
| (Department of Vasculocardiology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China;Laboratory of Phytomedicine and Disease Biochemistry, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China;Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201210, China) |
| 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. |
| Key words: diabetes mellitus diabetic cardiomyopathy salidroside Hippo signaling pathway inflammation |
