| 赵红霞,孟丽华,腾云鹏.盐酸纳美芬对心肌缺血再灌注大鼠缺氧诱导因子 1α/B细胞淋巴瘤 -2/E1B-19kDa相互作用蛋白 3通路及心肌自噬的影响[J].安徽医药,2021,25(12):2363-2368. |
| 盐酸纳美芬对心肌缺血再灌注大鼠缺氧诱导因子 1α/B细胞淋巴瘤 -2/E1B-19kDa相互作用蛋白 3通路及心肌自噬的影响 |
| Effects of nalmefene hydrochloride on Hif-1α/BNIP3 pathway and myocardial autophagy in rats with myocardial ischemia-reperfusion injury |
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| DOI：10.3969/j.issn.1009-6469.2021.12.008 |
| 中文关键词: 自噬 盐酸纳美芬 心肌再灌注 自噬相关蛋白质类 缺氧诱导因子 1，α亚基 Hif-1α/BNIP3通路 心肌自噬 大鼠， Sprague-Dawley |
| 英文关键词: Autophagy Nalmefene hydrochloride Myocardial reperfusion Autophagy-related proteins Hypoxia-Inducible factor 1, alpha subunit Hif-1α/BNIP3 pathway Myocardial autophagy Rats, Sprague-Dawley |
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| 中文摘要: |
| 目的探讨盐酸纳美芬对心肌缺血再灌注损伤( MIRI)大鼠缺氧诱导因子 1α(Hif-1α)/B细胞淋巴瘤 -2(Bcl-2)/E1B-19kDa相互作用蛋白 3(BNIP3)通路及心肌自噬的影响。方法 2020年 3—4月采用结扎冠状动脉左前降支法复制心肌缺血再灌注损伤( MIRI)大鼠模型，将造模成功的大鼠使用随机数字表法分成模型组、盐酸纳美芬低、中、高( 10 μg/kg、15 μg/kg、20 μg/kg)剂量组和氯喹组(阳性对照， 0.02 g/kg)，每组 15只，另取 15只假手术组大鼠作为对照。模型组和假手术组给予等剂量生理盐水，其余各组给予相对应剂量药物，每天 1次，连续 3d。给药结束 24 h后，氯化三苯基四氮唑( TTC)染色法检测心肌梗死面积；苏木精 -伊红(HE)染色观察心肌组织病理学变化；二氯荧光素双醋酸盐(DCFH-DA)法检测心肌组织中活性氧水平；蛋白质印迹法( Western blotting)检测心肌组织中自噬相关蛋白 Beclin1、LC3-Ⅰ、LC3-Ⅱ及通路蛋白 Hif-1α、BNIP3表达水平。结果假手术组大鼠心肌组织结构完整，无明显病理变化。与假手术组相比，模型组大鼠心肌组织结构异常、心肌细胞坏死、心肌损伤严重，心肌梗死面积、活性氧水平、 Beclin1、LC3-Ⅱ、Hif-1α、BNIP3蛋白表达水平和 LC3-Ⅱ/Ⅰ比值显著升高( P < 0.05)，其中 Hif-1α和 BNIP3蛋白表达水平分别为 0.92±0.11和 0.96±0.12，显著高于假手术组的 0.10±0.02和 0.08±0.01；与模型组相比，盐酸纳美芬低、中、高剂量组大鼠心肌组织病理损伤依次减轻，心肌梗死面积、活性氧水平、 Beclin1、LC3-Ⅱ、Hif-1α、BNIP3蛋白表达水平和 LC3-Ⅱ/Ⅰ比值依次降低( P < 0.05)，其中盐酸纳美芬高剂量组 Hif-1α和 BNIP3蛋白表达水平分别为 0.17±0.03和0.12±0.03，显著低于盐酸纳美芬中剂量组的 0.29±0.04和 0.31±0.05，盐酸纳美芬中剂量组显著低于盐酸纳美芬低剂量的 0.58±0.07和 0.52±0.08。盐酸纳美芬高剂量组与氯喹组大鼠各项指标差异无统计学意义( P > 0.05)。结论盐酸纳美芬可能通过抑制 Hif-1α/BNIP3通路，减弱 MIRI大鼠心肌自噬，缓解心肌损伤。 |
| 英文摘要: |
| Objective To investigate the effects of nalmefene hydrochloride on hypoxia-inducible factor-1α (Hif-1α)/Bcl-2 and ade. novirus E1B19kDa-interacting protein 3 (BNIP3) pathway and myocardial autophagy in rats with myocardial ischemia-reperfusion inju. ry (MIRI).Methods From March 2020 to April 2020, the MIRI rat model was established by ligating the left anterior descending coro.nary artery, the rats were randomly assigned into model group, low, medium and high dose nalmefene hydrochloride (10 μg/kg, 15 μg/kg, 20 μg/kg) groups and chloroquine group (positive control, 0.02g/kg), with 15 rats in each group, another 15 rats in sham operationgroup were taken as control. The model group and the sham operation group were given the same dose of normal saline, and the othergroups were given the corresponding dose of drugs, once a day for 3 consecutive days. At 24 hours after administration, the infarct sizewas measured by triphenyltetrazolium chloride (TTC) staining; HE staining was used to observe the pathological changes of myocardi.um; the level of reactive oxygen species in myocardium was measured by Dichlorofluorescein diacetate (DCFH-DA) method; Western blotting was used to detect the expression levels of autophagy related proteins Beclin1, LC3-Ⅰ, LC3-Ⅱ and pathway proteins Hif-1α, BNIP3.Results The myocardial tissue structure of sham operation group was intact without obvious pathological changes. Comparedwith those in the sham operation group, myocardial tissue structure abnormality, myocardial cell necrosis, severe myocardial injury,myocardial infarction area, reactive oxygen species level, Beclin1, LC3-Ⅱ, Hif-1α, BNIP3 protein expression levels and LC3-Ⅱ/Ⅰ ra. tio were significantly higher in the model group (P < 0.05), The expression levels of Hif-1α and BNIP3 protein were 0.92±0.11 and0.96±0.12, respectively, which were significantly higher than those of the sham operation group 0.10±0.02 and 0.08±0.01; comparedwith those in the model group, the pathological damage of myocardial tissue in the low, medium and high dose nalmefene hydrochloridegroups was alleviated in turn, myocardial infarction area, reactive oxygen species level, Beclin1, LC3-Ⅱ, Hif-1α, BNIP3 protein expres. sion levels and LC3-Ⅱ/Ⅰ ratio were decreased in turn (P < 0.05), among them, the expression levels of Hif-1α and BNIP3 protein in the high-dose nalmefene hydrochloride group were 0.17±0.03 and 0.12±0.03, respectively, which were significantly lower than those ofthe middle-dose nalmefene hydrochloride group 0.29±0.04 and 0.31±0.05, those in the middle-dose nalmefene hydrochloride group was significantly lower than those in the low-dose nalmefene hydrochloride 0.58±0.07 and 0.52±0.08; there was no significant differ. ence in the above indexes between the high-dose nalmefene hydrochloride group and chloroquine group (P > 0.05).Conclusion Na. lmefene hydrochloride may attenuate myocardial autophagy and alleviate myocardial injury in MIRI rats by inhibiting Hif-1α/BNIP3 pathway. |
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