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组织缺血分热缺血和冷缺血,热缺血时间和冷缺血时间属于外科移植范畴。热缺血时间是指器官从供体供血停止到冷灌注开始的这段时间。这一期间对器官的损害最为严重,一般不应超过10分钟,这是因为热缺血时,虽然血流中断,但是器官组织仍继续进行代谢。此时,因氧和各种代谢底物供应缺乏但器官组织的代谢水平仍高,所以器官缺血损害出现较快、程度较重,又因氧消耗完后,仍可进行无氧代谢,但代谢产物无法清除,可引起酸中毒,代谢必需的养料和酶系统亦有消耗。冷缺血时间是器官从冷灌注开始到移植后供血开始的这段时间。热缺血时间导致的器官损伤为热缺血损伤,而冷缺血时间发生的损伤为冷缺血损伤。
氢气具有选择性抗氧化作用,尤其是对组织缺血再灌注损伤具有理想的保护作用,器官移植也存在组织缺血再灌注损伤,因此也是氢气治疗研究的重要疾病类型,这方面研究最多也最深入的是美国匹兹堡大学器官移植中心。他们先后证明呼吸氢气和饮用氢水对小肠、肾脏、肝脏、心脏、肺脏等器官移植后急性和慢性损伤具有保护作用。国内开展大量氢气生物学研究,但在器官移植方面的研究相对比较少,曾经有学者进行过肾脏移植和心脏体外保护方面的研究。
最近哈尔滨医科大学发表氢气灌流对体外肺组织保护,或者氢气对冷缺血损伤保护效应的研究。研究用氢气氧气混合气中氢气的浓度为3%,灌流的总体积为每公斤5毫升,气体每20分钟更新一次,持续2小时。检测指标保护肺组织干湿比,氧化损伤指标,血清和组织炎症因子,组织细胞凋亡等。研究结果表明,氢气对肺冷缺血损伤具有保护作用。
ExpBiol Med (Maywood). 2015 Feb 7. pii: 1535370214563895.
Lung inflation with hydrogen during the cold ischemia phase decreases lung graftinjury in rats. LiuR1, Fang X1, Meng C1, Xing J1, Liu J1, Yang W1, Li W2, Zhou H3.
Hydrogen has antioxidant and anti-inflammatory effects on lung ischemia-reperfusioninjury when it is inhaled by donor or/and recipient. This study examined the effects of lung inflation with 3% hydrogen during the cold ischemia phase on lung graft function in rats. The donor lung was inflated with 3% hydrogen, 40% oxygen, and 57% nitrogen at 5 mL/kg, and the gas was replaced every 20 minduring the cold ischemia phase for 2 h. In the control group, the donor lungwas inflated with 40% oxygen and 60% nitrogen at 5 mL/kg. The recipient waseuthanized 2 h after orthotropic lung transplantation. The hydrogenconcentration in the donor lung during the cold ischemia phase was 1.99-3%. The oxygenation indices in the arterial blood and pulmonary vein blood were improved in the hydrogen group. The inflammation response indices, including lung W/D ratio, the myeloper oxidase activity in the grafts, and the levels ofIL-8 and TNF-α in serum, were significantly lower in the hydrogen group(5.2 ± 0.8, 0.76 ± 0.32 U/g, 340 ± 84 pg/mL, and 405 ± 115 pg/mL, respectively) than those in the control group (6.5 ± 0.7, 1.1 ± 0.5 U/g, 443 ± 94 pg/mL, and657 ± 96 pg/mL, respectively (P < 0.05), and the oxidative stress indices,including the superoxide dismutase activity and the level of malonaldehyde inlung grafts were improved after hydrogen application. Furthermore, the lunginjury score determined by histopathology, the cell apoptotic index, and thecaspase-3 protein expression in lung grafts were decreased after hydrogentreatment, and the static pressure-volume curve of lung graft was improved byhydrogen inflation. In conclusion, lung inflation with 3% hydrogen during thecold ischemia phase alleviated lung graft injury and improved graft function.
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