Deficiency of Mitochondrial Functions and Peroxidation of Frontoparietal Cortex Enhance Isoflurane Sensitivity in Aging Mice.
Deficiency of Mitochondrial Functions and Peroxidation of Frontoparietal Cortex Enhance Isoflurane Sensitivity in Aging Mice.
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线粒体功能缺陷和额顶皮层过氧化增强衰老小鼠的异氟烷敏感性
DOI：
10.3389/fnagi.2020.583542
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发表时间：
2020
影响因子：
4.8
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Gong C;Zhang D;Ou W;Ou M;Liang P;Liao D;Zhang W;Zhu T;Liu J;Zhou C
背景：对全麻过敏可能预示着不良的术后预后，尤其是在老年患者中。因此，有必要阐明老年人对挥发性麻醉药过敏的机制。鉴于异氟烷敏感性随年龄增长而增加的事实，我们假设线粒体功能缺陷和额顶叶皮层氧化水平升高可能导致衰老小鼠对异氟烷敏感性增强。方法：测定衰老小鼠对异氟醚的敏感性，采用恢复翻正反射（LORR）所需的异氟醚浓度。使用海马XFp分析仪测量额顶叶皮层线粒体生物能量学。分别采用Oxyblot蛋白氧化检测试剂盒和硫代巴比妥酸活性物质（TBARS）法评估额顶叶皮层蛋白氧化和脂质氧化。在体内测试了丙二酸抑制线粒体复合体II和臭氧过氧化作用对异氟烷敏感性的影响。此外，还测定了抗氧化治疗对小鼠线粒体功能和异氟醚敏感性的影响。结果：老龄小鼠（14 ~ 16月龄）LORR所需异氟醚平均浓度为0.83%±0.13% （mean±SD, n = 80）。然后，根据LORR所需异氟醚浓度将小鼠分为敏感组（S组，均值−SD）、中等组（M组）和耐药组（R组，均值+ SD） 3组。S组小鼠线粒体复合体II和复合体IV活性明显低于R组，而S组小鼠额顶叶皮质丙二醛（MDA）水平较高。线粒体复合物的抑制和过氧化作用都显著降低了体内LORR所需的异氟烷浓度。经地贝酮处理后，衰老小鼠脂质氧化水平减轻，线粒体功能恢复。依地苯酮治疗后，LORR所需的异氟烷浓度也升高。结论：衰老小鼠的线粒体功能下降和额顶叶皮层氧化应激水平升高可能与异氟烷过敏有关。
Background: Hypersensitivity to general anesthetics may predict poor postoperative outcomes, especially among the older subjects. Therefore, it is essential to elucidate the mechanism underlying hypersensitivity to volatile anesthetics in the aging population. Given the fact that isoflurane sensitivity increases with aging, we hypothesized that deficiencies of mitochondrial function and elevated oxidative levels in the frontoparietal cortex may contribute to the enhanced sensitivity to isoflurane in aging mice. Methods: Isoflurane sensitivity in aging mice was determined by the concentration of isoflurane that is required for loss of righting reflex (LORR). Mitochondrial bioenergetics of the frontoparietal cortex was measured using a Seahorse XFp analyzer. Protein oxidation and lipid oxidation in the frontoparietal cortex were assessed using the Oxyblot protein oxidation detection kit and thiobarbituric acid reactive substance (TBARS) assay, respectively. Contributions of mitochondrial complex II inhibition by malonate and peroxidation by ozone to isoflurane sensitivity were tested in vivo. Besides, effects of antioxidative therapy on mitochondrial function and isoflurane sensitivity in mice were also measured. Results: The mean concentration of isoflurane that is required for LORR in aging mice (14–16 months old) was 0.83% ± 0.13% (mean ± SD, n = 80). Then, the mice were divided into three groups as sensitive group (S group, mean − SD), medium group (M group), and resistant group (R group, mean + SD) based on individual concentrations of isoflurane required for LORR. Activities of mitochondrial complex II and complex IV in mice of the S group were significantly lower than those of the R group, while frontoparietal cortical malondialdehyde (MDA) levels were higher in the mice of S group. Both inhibition of mitochondrial complexes and peroxidation significantly decreased the concentration of isoflurane that is required for LORR in vivo. After treatment with idebenone, the levels of lipid oxidation were alleviated and mitochondrial function was restored in aging mice. The concentration of isoflurane that required for LORR was also elevated after idebenone treatment. Conclusions: Decreased mitochondrial functions and higher oxidative stress levels in the frontoparietal cortex may contribute to the hypersensitivity to isoflurane in aging mice.
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影响因子：
5.3
作者：
Jacob, Kimberly D.;Noren Hooten, Nicole;Trzeciak, Andrzej R.;Evans, Michele K.
通讯作者：
Evans, Michele K.
影响因子：
5.7
作者：
Fritz BA;Kalarickal PL;Maybrier HR;Muench MR;Dearth D;Chen Y;Escallier KE;Ben Abdallah A;Lin N;Avidan MS
通讯作者：
Avidan MS
影响因子：
2.8
作者：
Brailovskaya, IV;Starkov, AA;Mokhova, EN
通讯作者：
Mokhova, EN
影响因子：
6.1
作者：
Ma, Jie-Qiong;Luo, Rong-Zhen;Liu, Chan-Min
通讯作者：
Liu, Chan-Min
DOI：
10.1093/gerona/55.9.b448
发表时间：
2000-09-01
影响因子：
5.1
作者：
Magnusson, KR;Scanga, C;Dunlop, C
通讯作者：
Dunlop, C