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异氟烷会增加非妊娠大鼠血管基质金属蛋白酶-2 的活性,并增加妊娠期间的一氧化氮代谢物。

Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy.

机构信息

Department of Biophysics and Pharmacology, Institute of Biosciences of Botucatu, Sao Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.

School of Veterinary Medicine and Animal Science, UNESP, Botucatu, Sao Paulo, Brazil.

出版信息

Biosci Rep. 2024 Jun 26;44(6). doi: 10.1042/BSR20240192.

Abstract

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.

摘要

需要全身麻醉的手术在妊娠中发生的概率为 1.5%-2%。由于异氟醚降低了对胎儿生长的影响,因此常被用于该手术。因此,我们检测了异氟醚麻醉对母体血液动力学和血管变化的影响。我们假设异氟醚会增加一氧化氮并降低金属蛋白酶(MMPs),从而增强内皮依赖性血管舒张。将 28 只雌性大鼠随机分为 4 组(每组 7 只):清醒(未麻醉)非妊娠组、非妊娠麻醉组、妊娠组、妊娠麻醉组。在妊娠第 20 天进行麻醉,并监测血液动力学参数。检测了一氧化氮代谢物、MMP-2 和 MMP-9 的凝胶酶活性以及血管功能。与非妊娠麻醉组相比,异氟醚对妊娠大鼠的血液动力学没有显著影响。仅在清醒非妊娠组观察到乙酰胆碱诱导的松弛作用明显减弱(约 62%),而其他组则为 81%。与非妊娠组相比,两组妊娠组去内皮主动脉段的苯肾上腺素诱导的收缩作用更强(无论是否使用异氟醚)。与其他组相比,麻醉妊娠组的一氧化氮代谢物更高。与清醒非妊娠组相比,麻醉妊娠(或未麻醉)组的主动脉中 75 kDa 活性降低,同时 64 kDa MMP-2 同工型增加。异氟醚麻醉对妊娠血液动力学参数和 MMP-2 的正常激活有稳定的影响。此外,一氧化氮的生物利用度增加,提示异氟醚在妊娠期间对内皮有保护作用。

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