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| 尼可地尔对单肺通气中塌陷肺组织缺氧诱导因子1α的影响 |
| Effects of nicorandil on the expression of hypoxia-inducible factor 1α in lung tissue of one-lung ventilation |
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| DOI：10.12089/jca.2018.01.018 |
| 中文关键词: 尼可地尔 单肺通气 肺保护 超氧化物歧化酶 缺氧诱导因子-1α |
| 英文关键词: Nicorandil One-lung ventilation Lung protection Superoxide dismutase Hypoxia-inducible factor-1α |
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| 中文摘要: |
| 目的 尼可地尔对单肺通气中塌陷肺组织缺氧诱导因子(hypoxia-inducible factor,HIF)-1α（HTF-1α）表达的影响。方法 选用清洁级新西兰白兔24只，随机分为sham组(S组,双肺通气+开胸)、阴性对照组(C组,单肺通气+开胸+生理盐水)、尼可地尔组(N组,单肺通气+开胸+尼可地尔)、拮抗剂组(J组,单肺通气+开胸+尼可地尔+格列苯脲),每组6只。麻醉诱导后,行气管切开置入自制双腔气管导管实施机械通气。S组仅麻醉手术,不单肺通气,其他三组均有单双肺通气,并在手术开始前输注干预药物。N组在单肺通气前由静脉输入尼可地尔100 μg·kg-1·h-1,输注1 h。C组输注等量生理盐水。J组在实施单肺通气前由静脉输入格列苯脲75 μg·kg-1·h-1及尼可地尔100 μg·kg-1·h-1,输注1 h。取非通气肺保存处理,测湿/干重比(W/D)和SOD活性。采用Western blot法检测非通气肺组织HIF-1α蛋白含量,实时定量PCR(qRT-PCR)法检测非通气肺组织HIF-1α mRNA表达量。结果 C组和J组非通气侧肺W/D明显高于，SOD活性明显低于S组和N组(P<0.05)。C组、N组和J组HIF-1α蛋白和HIF-1α mRNA表达量明显高于S组,且N组明显高于C组和J组(P<0.05)。结论 尼可地尔在家兔单肺通气时对非通气侧肺有保护作用,减少氧化应激,并且作用于mito KATP,通过上调HIF-1α发挥作用。 |
| 英文摘要: |
| Objective To investigate the effects of nicorandil on hypoxia-inducible factor (HIF)-1α mRNA and protein in lung tissue of one-lung ventilation. Methods Twenty-four clean New Zealand white rabbits were randomly divided into sham group (group S) (two-lung ventilation+thoracotomy), negative control group (group C) (one-lung ventilation+thoracotomy+saline), nicorandil group (group N) (one-lung ventilation+thoracotomy+nicorandil) and antagonist group (group J) (one-lung ventilation+thoracotomy+nicorandil+glibenclanide) equally. The implementation of mechanical ventilation depended on self-made double-lumen endotracheal tube after intravenous induction through ear marginal vein. Intravenous maintenance medicine was infused by trace injection pump after anesthesia induction. The implementation of thoracic surgery was simulated through one-lung and two-lung ventilation by auscultation, bubble test and direct observation. Group S was given anaesthesia only, no one-lung ventilation group S, the other three groups had single lung ventilation, and the drug was injected before the operation. Group N was infused nicorandil 100 μg·kg-1·h-1 before the implementation of single lung ventilation for 1 h. Group C was injected with the same amount of normal saline. Group J was intravenous infusion of glibenclamide 75 μg·kg-1·h-1 and nieorandil 100 μg·kg-1·h-1 the implementation of single lung ventilation for 1 h. Then wet and dry weight ratio(W/D) and superoxide dismutase (SOD) activity were measured after non-ventilatory lung was processed and preserved. The expression of HIF-1α protein of non-ventilatory lung tissue was detected by Western-blot in the four groups. The transcription of HIF-1α mRNA was detected by real-time quantitative real-time PCR (qRT-PCR) in all groups. Results W/D in groups C and J were significantly higher compared with that of groups S and N (P<0.05). The activity of SOD in groups C and J was significantly lower compared with groups S and N (P<0.05). The expression of HIF-1α protein and transcription of HIF-1α mRNA in groups C, N and J were significantly higher than those in group S, and that of group N was significantly higher than those of groups C and J (P<0.05). Conclusion Nicorandil has a protective effect on the collapse and inflation of non ventilatory lung in rabbit with one-lung ventilation, reducing oxidative stress by SOD, acting on mito KATP and coming into play by up-regulation of HIF-1α. |
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