目的 在肝缺血再灌注小鼠模型中研究甲烷对肝线粒体的影响。方法 将C57小鼠18只随机分为空白对照组(SHAM组)、缺血再灌注组(IR组)和甲烷盐水治疗组(IR+CH4组),每组6只,采用70%肝缺血再灌注模型,IR+CH4组再灌注开始前予甲烷生理盐水10 ml/kg腹腔内注射,留取标本检测氧化、抗氧化、线粒体相关指标。结果 与IR组相比,IR+CH4降低了ROS水平(t=3.154,P=0.0083)及MDA(t=3.738, P=0.028)水平,提高了GSH(t=2.687, P=0.0177)及SOD(t=3.480, P=0.0037)水平;采用Westen blot 检测蛋白的表达,与对照组相比,IR组线粒体融合蛋白Mfn1(q=7.57,P＜0.05)和OPA1(q=6.41,P＜0.05)表达减少,分裂蛋白DLP1(q=3.718,P＜0.05)表达增加;与IR组相比,IR+CH4组融合蛋白Mfn1(q=5.277, P＜0.05)增加,分裂蛋白DLP1(q=6.700,P＜0.05)表达下降;IR组PINK1(q=4.606, P＜0.05)表达上调,IR+CH4组PINK1(q=3.922, P＜0.05)表达下降。结论 甲烷生理盐水可降低氧化应激,提高机体抗氧化能力,促进线粒体融合,减少分裂,促进线粒体功能的恢复。
Abstract
Objective To study the effect of methane on liver mitochondria in a mouse model of liver ischemia reperfusion.Methods C57 mice were randomly divided into the blank control group (SHAM group n=6), ischemia-reperfusion group ( IR group n=6 ) and methane-rich saline treatment group (IR+CH4 group n=6). The 70% liver ischemia-reperfusion model was adopted. Methane-rich saline 10ml/kg was injected intraperitoneally before reperfusion in the IR+CH4 group. Samples were taken to detect oxidation, antioxidation and mitochondrium related indexes.Results Methane-rich saline increased SOD(t=3.480, P=0.0037)/(GSHt=2.687, P=0.0177) levels but decreased MDA(t=2.771, P=0.015)/ROS(t=3.154, P=0.0083) levels. In the IR group, the expressions of mitochondrial fusion proteins Mfn1(q=7.57,P<0.05) and OPA1(q=6.41,P<0.05) decreased while the expression of mitogen DLP1(q=3.718,P<0.05) increased. PINK1 expression was up-regulated in the IR group (q=4.606,P<0.05)and down-regulated in the IR+CH4 group(q=3.922,P<0.05).Conclusions Methane-rich saline can improve the body’s antioxidant capacity, promote mitochondrial fusion, reduce mitochondrion, and boost the recovery of mitochondrial function.
关键词
甲烷 /
线粒体 /
肝脏缺血再灌注损伤 /
线粒体自噬
Key words
methane /
mitochondrium /
hepatic ischemia reperfusion injury /
mitochondrial autophagy
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Keppler F, Hamilton J T, Braβ M, et al. Methane emissions from terrestrial plants under aerobic conditions [J] . Nature, 2006, 439(7073):187-191.
[2] Wang Z P, Gulledge J, Zheng J Q, et al. Physical injury stimulates aerobic methane emissions from terrestrial plants[J]. Biogeosciences, 2009, 6:615-621.
[3] Keppler F, Hamilton J T, McRoberts W C, et al.Methoxyl groups of plant pectin as a percursor of atmospheric methane: evidencedromdeuterium l abelling studies[J]. New Phytol, 2008, 178: 808-814.
[4] Ghyczy M, Torday C, Kaszaki J, et al. Hypoxia-Induced generation of methane in mitochondria and eukaryotic cells-an alternative approach to methanogenesis[J]. Cell Physiol Biochem, 2008,21(3):251-258.
[5] Tuboly E, Szabo A, Garab D, et al. Methane biogenesis during sodium azide-induced chemical hypoxia in rats[J]. Am J Physiol Cell Physiol, 2013,304(2): C207-214.
[6] Wishkerman A, Greiner S, Ghyczy M, et al. Enhanced formation of methane in plant cell cultures by inhibition of cytochrome c oxidase[J]. Plant Cell Environ, 2011, 34(3): 457-64.
[7] Tuboly E, Molnar R, Tokes T, et al. Excessive alcohol consumption induces methane production in humans and rats[J]. Sci Rep,2017, 7(1):7329.
[8] Ye Z, Chen O, Zhang R, et al. Methane attenuates hepatic ischemia/reperfusion injury in rats through antiapoptotic, anti-inflammatory, and antioxidative actions[J]. Shock, 2015, 44(2): 181-187.
[9] Meng Y, Jiang Z, LiN,et al. Protective effects of methane-rich saline on renal ischemic-reperfusion injury in a mouse model[J]. Med Sci Monitor, 2018, 24: 7794-7801.
[10] Chen O, Ye Z, Cao Z, et al.Methane attenuates myocardial ischemia injury in rats through anti-oxidative, anti-apoptotic and anti-inflammatory actions[J].Free Radic Biol Med,2016,90: 1-11.
[11] Liu L, Sun Q, Wang R, et al. Methane attenuates retinal ischemia/reperfusion injury via anti-oxidative and anti-apoptotic pathways[J]. Brain Res, 2016, 1646: 327-333.
[12] Wang W, Huang X, Li J, et al. Methane suppresses microglial activation related to oxidative, inflammatory, and apoptotic injury during spinal cord injury in rats[J]. Oxid Med Cell Longev, 2017: 2190897.
[13] Boros M, Ghyczy M, rces D, et al. The anti-inflammatory effects of methane[J]. Crit Care Med,2012, 40: 1269-1278.
[14] Adam-Vizi V, Chinopoulos C. Bioenergetics and the formation of mitochondrial reactive oxygen species[J]. Trends Pharmacol Sci,2006, 27(12): 639-645.
[15] Miller K W, Hammond L, Porter E G. The solubility of hydrocarbon gases in lipid bilayers[J]. Chem Phys Lipids,1977, 20: 229-241.
[16] Meyer M, Tebbe U, Piiper J. Solubility of inert gases in dog blood and skeletal muscle[J]. Pflugers Arch,1980, 384:131-134.
[17] Koyano F, Okatsu K, Kosako H, et al. Ubiquitin is phosphorylated by PINK1 to activate parkin[J]. Nature, 2014, 510(7503): 162-166.
PDF(777 KB)
