| 夏丽秀,尹霞,肖瑞.金丝桃苷通过调控微 RNA-125a-5p/信号传导和转录激活因子 3轴减轻脑缺血 /再灌注损伤[J].安徽医药,2023,27(7):1317-1323. |
| 金丝桃苷通过调控微 RNA-125a-5p/信号传导和转录激活因子 3轴减轻脑缺血 /再灌注损伤 |
| Hyperin reduces cerebral ischemia / reperfusion injury via regulating miR-125a-5p / STAT3 axis |
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| DOI：10.3969/j.issn.1009-6469.2023.07.010 |
| 中文关键词: 金丝桃苷 缺血 /再灌注 微 RNA-125a-5p 信号传导和转录激活因子 3 |
| 英文关键词: Hyperin Ischemia/Reperfusion miR-125a-5p Signal transducer and activator of transcription3 |
| 基金项目:湖北省自然科学基金项目( 2019CFB398) |
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| 中文摘要: |
| 目的探讨金丝桃苷调控微 RNA-125a-5p(miR-125a-5p)/信号传导和转录激活因子 3(STAT3)轴对脑缺血 /再灌注(ischemia/reperfusion，I/R)损伤的影响。方法通过 GEO数据库筛选脑 I/R损伤的差异表达基因。于 2021年 6月至 2022年 1月建立大鼠 I/R模型并将其分为假手术组、模型组、金丝桃苷低剂量组( 20 mg/kg)、金丝桃苷高剂量组( 50 mg/kg)。通过氧 -葡萄糖剥夺 /复氧(OGD/R)法建立 I/R细胞模型。实时荧光定量 PCR(qRT-PCR)检测组织与细胞中 miR-125a-5p、STAT3的表达的情况。酶联免疫吸附法(ELISA)试剂盒检测细胞上清液中炎性因子白细胞介素 -6(IL-6)、肿瘤坏死因子 -α(TNF-α)的水平。乳酸脱氢酶(LDH)和超氧化物歧化酶( SOD)试剂盒分别检测细胞的抗氧化能力。结果金丝桃苷在脑 I/R损伤大鼠中起保护作用。相对于假手术组( 1±0.09、1±0.08、0.67±0.06)模型组大鼠脑组织中 miR-125a-5p表达( 0.21±0.03)降低、 STAT3的 mRNA(4.89±0.52)和蛋白表达( 2.25±0.24)水平升高。金桃苷能够促进 miR-125a-5p的表达并抑制 STAT3的表达。细胞实验中，与对照组比较， OGD/R组 miR-125a-5p表达被抑制， IL-6、TNF-α浓度增强， SOD活性下降而 LDH活性增加，加入金丝桃苷后上述指标表达被部分逆转。但是金丝桃苷对 I/R细胞模型的保护作用能够被 miR-125a-5p inhibitor和 STAT3过表达部分挽救。结论 丝金丝桃苷在 I/R动物和细胞模型中均具有保护作用，而该作用可能是通过调控 miR-125a-5p/STAT3轴实现的。 |
| 英文摘要: |
| Objective To investigate the effects of Hyperin on cerebral ischemia/reperfusion (I/R) injury through regulating microRNA-125A-5p (miR-125a-5p)/ signal transducer and activator of transcription3 (STAT3).Methods GEO database was used to screen the differentially expressed genes of brain I/R injury. The I/R rat model was established from June 2021 to January 2022 and divided into sham operation group, model group, hypericin low-dose group (20 mg/kg) and hypericin high-dose group (50 mg/kg). I/R cell model was established by hypoxia-glucose deprivation and re-oxygenation (OGD/R). Real-time quantitative fluorescence PCR (qRT-PCR) was used to detect the expression of miR-125a-5p and STAT3 in tissues and cells. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the level of inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the supernatant fluid. Theantioxidant capacity was evaluated by lactate dehydrogenase (LDH) and superoxide dismutase (SOD) kits.Results Hyperin showed protective effect in rats with brain I/R injury. Compared with sham operation group (1±0.09、1±0.08、0.67±0.06), the expression of miR-125a-5p was decreased (0.21±0.03), mRNA (4.89±0.52) and protein levels (2.25±0.24) of STAT3 were increased in brain tissue ofrats in model group. Hyperin promoted the expression of miR-125a-5p while inhibited the expression of STAT3. In cell experiments, compared with control group, the expression of miR-125a-5p was inhibited, the concentrations of IL-6 and TNF-α were increased, theactivity of SOD was decreased and the activity of LDH was increased in OGD/R group, and the expression of these indexes was partiallyreversed after hypericin was added. However, the protective effects of Hyperin on I/R cell models could be partially saved by miR-125a5p inhibitor and STAT3 overexpression.Conclusion Hyperin has a protective effects in both I/R animal and cell models, and this effects may be realized through regulation of miR-125a-5p/STAT3 axis. |
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