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类叶升麻苷调控Rnd3/NF-κB通路对缺氧/复氧诱导心肌细胞损伤的影响
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| 篇名： | 类叶升麻苷调控Rnd3/NF-κB通路对缺氧/复氧诱导心肌细胞损伤的影响 |
| TITLE： | Effects of acteoside on hypoxia/reoxygenation-induced cardiomyocyte damage by regulating the Rnd 3/NF-κB pathway |
| 摘要： | 目的 探讨类叶升麻苷调控Rho家族GTP酶3（Rnd3）/核因子κB（NF-κB）通路对缺氧/复氧（H/R）诱导心肌细胞损伤的影响。方法本实验将H9c2心肌细胞分为对照组（不给药、不造模）、H/R组（仅造模）、H/R+AS-L组、H/R+AS-M组、H/R+AS-H组（以上3组先分别给予10、30、90μmol/L类叶升麻苷，再造模）、H/R+pcDNA组[先转染pcDNA（空载体），再造模]、H/R+pcDNA-Rnd3组[先转染pcDNA-Rnd3（Rnd3过表达载体）使Rnd3过表达，再造模]、H/R+AS-H+si-NC组[先转染si-NC（阴性对照），然后给予90μmol/L类叶升麻苷，再造模]、H/R+AS-H+si-Rnd3组[先转染si-Rnd3（Rnd3小分子干扰RNA）抑制Rnd3过表达，然后给予90μmol/L类叶升麻苷，再造模]。各组经相应处理后，检测细胞凋亡率和细胞中乳酸脱氢酶（LDH）释放量、丙二醛（MDA）水平、超氧化物歧化酶（SOD）活性、肿瘤坏死因子α（TNF-α）水平、白细胞介素1β（IL-1β）水平、IL-6水平、Rnd3和NF-κB亚基p65（NF-κBp65）mRNA及蛋白的表达、活化胱天蛋白酶3（CleavedCaspase-3）和CleavedCaspase-9蛋白表达的变化。结果给予不同浓度类叶升麻苷均可降低H/R诱导H9c2心肌细胞凋亡率、CleavedCaspase-3和CleavedCaspase-9蛋白表达水平、NF-κBp65mRNA及蛋白表达水平、LDH释放量和MDA、TNF-α、IL-1β、IL-6水平，升高SOD活性和Rnd3mRNA及蛋白表达水平（P＜0.05），且呈剂量依赖性。Rnd3过表达可使H/R诱导H9c2心肌细胞凋亡率，NF-κBp65、CleavedCaspase-3、CleavedCaspase-9蛋白表达水平，LDH释放量和MDA、TNF-α、IL-1β、IL-6水平降低，使Rnd3蛋白表达水平和SOD活性升高（P＜0.05）；而抑制Rnd3过表达，可减弱类叶升麻苷对H/R诱导H9c2心肌细胞的凋亡、氧化应激及炎症反应的抑制作用（P＜0.05）。结论类叶升麻苷可通过促进Rnd3表达、抑制NF-κBp65表达来调控Rnd3/NF-κB通路，进而抑制心肌细胞凋亡、氧化应激及炎症反应，从而减轻H/R诱导的心肌细胞损伤。 |
| ABSTRACT： | OBJECTIVE To explore the effects of acteoside on hypoxia/reoxygena tion（H/R）-induced cardiomyocyte damage by regulating Rho family GTPase 3（Rnd3）/nuclear factor κB（NF-κB）pathway. METHODS The H 9c2 cardiomyocyte were divided into control group （no administration ，no modeling ），H/R group （only modeling ），H/R+AS-L group ，H/R+AS-M group ， H/R+AS-H group （10，30，90 μmol/L acteoside for above 3 groups firstly ，and then modeling ），H/R+pcDNA group [transfecting pcDNA （empty vector ） firstly，and then modeling] ，H/R + pcDNA-Rnd 3 group [overexpression of Rnd 3 by transfecting pcDNA-Rnd3（Rnd3 overexpression vector ）firstly，and then modeling] ，H/R+AS-H+si-NC group [transfecting si-NC （negative control）firstly，and then giving 90 μmol/L acteoside and modeling]，H/R+AS-H+si-Rnd3 group [inhibiting overexpression of Rnd 3 by transfecting si-Rnd 3 （Rnd3 small interfering RNA ） firstly，and then giving 90 μ mol/L acteoside and modeling]. After corresponding treatment ，the apoptotic rate ，release of lactate dehydrogenase （LDH），malondialdehyde（MDA）level，the activity of superoxide dismutase （SOD），the level of tumor necrosis factor α（TNF-α），interleukin 1β（IL-1β）and interleukin- 6（IL-6）， mRNA and protein expression of Rnd 3 and NF-κB subunit p65（NF-κB p65），the expression of aspartate proteolytic enzyme 3 （Cleaved Caspase- 3）protein and Cleaved Caspase- 9 protein were detected. RESULTS Different concentrations of acteoside could reduce the apoptotic rate of H/R-induced H 9c2 cardiomyocyte，the protein expressions of Cleaved Caspase- 3 and Cleaved Caspase-9，mRNA and protein expressions of NF-κB p65，the levels of LDH release and MDA ，TNF-α，IL-1β and IL-6，while increase the activity of SOD and mRNA and protein expressions of Rnd 3（P＜0.05），in a dose-dependent manner. Overexpression of Rnd 3 could decrease the apoptotic rate of H 9c2 cardiomyocyte，protein expressions of NF-κB p65，Cleaved Caspase- 3 and Cleaved Caspase- 9， the levels of LDH release ， MDA， TNF-α，IL-1β and IL-6，while increase the protein expression of Rnd 3 and the activity of SOD （P＜0.05）. The inhibition overexpression of Rnd 3 could weaken the inhibitory effects of acteoside on H/R-induced apoptosis of H 9c2 cardiomyocyte， oxidative stress and inflammatory reaction （P＜0.05）. CONCLUSIONS Acteoside could regulate Rnd 3/NF-κ B pathway by promoting the expression of Rnd 3 and inhibiting the expression of NF-κB p65，inhibit cardiomyocyte apoptosis ，oxidative stress and inflammation reaction so as to relieve the H/R-induced cardiomyocyte damage. |
| 期刊： | 2022年第33卷第05期 |
| 作者： | 杨洋，李天发，王军，黄珊，凌学斌 |
| AUTHORS： | YANG Yang，LI Tianfa ，WANG Jun，HUANG Shan，LING Xuebin |
| 关键字： | 类叶升麻苷；Rnd3/NF-κB通路；缺氧/复氧；H9c2心肌细胞；细胞凋亡；氧化应激；炎症反应 |
| KEYWORDS： | acteoside；Rnd3/NF-κB pathway；hypoxia/reoxygenation；H9c2 cardiomyocyte；cell apoptosis ；oxidative stress ； |
| 阅读数： | 188 次 |
| 本月下载数： | 4 次 |
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