Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver
Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver
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DOI：
10.1007/s00595-014-1064-4
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发表时间：
2015-07-01
期刊：
影响因子：
2.5
通讯作者：
Todo, Satoru
中科院分区：
文献类型：
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作者：
Shimada, Shingo;Fukai, Moto;Todo, Satoru
硫化氢（H2S）可改善肝脏缺血再灌注损伤（IRI），但其确切机制尚不清楚。我们研究了硫化氢钠（NaHS）， H2S的可溶性衍生物，是否会改善肝脏IRI，如果是，通过什么机制。小鼠局部热缺血75 min后再灌注。再灌注前10分钟静脉给予NaHS或生理盐水。再灌注后3、6、24 h采集肝脏和血清。在NaHS（-）组中，严重的IRI表现为ALT渗漏、组织损伤评分、细胞凋亡、脂质过氧化和炎症（血浆tnf - α、IL-6、IL-1 β、ifn - γ、IL-23、IL-17和CD40L升高），而NaHS（+）组的IRI明显改善。这些影响可以通过Nrf2核易位的增加以及HO-1和硫氧还蛋白-1的上调来解释。已知介导促生存和抗凋亡信号的PDK-1/Akt/mTOR/p70S6k轴的磷酸化在NaHS（+）组中显著增强，此后pna阳性细胞率更高。NaHS通过直接和间接的抗氧化活性改善肝脏IRI，通过涉及Nrf-2的机制增强促生存、抗凋亡和抗炎信号，并通过涉及Akt-p70S6k的机制加速肝脏再生。
Hydrogen sulfide (H2S) ameliorates hepatic ischemia and reperfusion injury (IRI), but the precise mechanism remains elusive. We investigated whether sodium hydrogen sulfide (NaHS), a soluble derivative of H2S, would ameliorate hepatic IRI, and if so, via what mechanism.Mice were subjected to partial warm ischemia for 75 min followed by reperfusion. Either NaHS or saline was administered intravenously 10 min before reperfusion. The liver and serum were collected 3, 6, and 24 h after reperfusion.In the NaHS(-) group, severe IRI was apparent by the ALT leakage, tissue injury score, apoptosis, lipid peroxidation, and inflammation (higher plasma TNF-alpha, IL-6, IL-1 beta, IFN-gamma, IL-23, IL-17, and CD40L), whereas IRI was significantly ameliorated in the NaHS(+) group. These effects could be explained by the augmented nuclear translocation of Nrf2, and the resulting up-regulation of HO-1 and thioredoxin-1. Phosphorylation of the PDK-1/Akt/mTOR/p70S6k axis, which is known to mediate pro-survival and anti-apoptotic signals, was significantly augmented in the NaHS(+) group, with a higher rate of PCNA-positive cells thereafter.NaHS ameliorated hepatic IRI by direct and indirect anti-oxidant activities by augmenting pro-survival, anti-apoptotic, and anti-inflammatory signals via mechanisms involving Nrf-2, and by accelerating hepatic regeneration via mechanisms involving Akt-p70S6k.