Hydrogen sulfide prevents renal ischemia-reperfusion injury in CLAWN miniature swine
Hydrogen sulfide prevents renal ischemia-reperfusion injury in CLAWN miniature swine
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硫化氢预防 CLAWN 小型猪肾缺血再灌注损伤
DOI：
10.1016/j.jss.2017.05.123
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发表时间：
2017
影响因子：
2.2
通讯作者：
Yamada Kazuhiko
中科院分区：
文献类型：
--
作者：
Sekijima Mitsuhiro;Sahara Hisashi;Miki Katsuyuki;Villani Vincenzo;Ariyoshi Yuichi;Iwanaga Takehiro;Tomita Yusuke;Yamada Kazuhiko
最近有报道称硫化氢（H2S）具有抗炎和细胞保护作用；然而，其功效尚未在大型动物模型中得到很好的证明。在这项研究中，我们在临床前微型猪模型中研究了H2S是否对肾缺血再灌注损伤（IRI）具有细胞保护作用。方法：主要组织相容性复合体近交系的CLAWN微型猪（n= 9）行右肾切除术，然后通过在左肾动静脉上放置夹子诱导120分钟的热缺血。1组（n= 3）肾缺血，不给H2S。2组（n= 3）、3组（n= 3）缺血肾再灌注前10 min给予Na2S （H2S前体药），再灌注后30 min静脉给予Na2S（2组）或经左肾动脉选择性给予Na2S（3组）。通过肾活检、血清和肾组织中的炎症细胞因子水平来评估IRI。结果1组动物血清肌酐水平显著高于2、3组（P< 0.01）。术后第2天，组织学显示1组肾小管损伤严重，tunel阳性细胞较多，2组损伤较轻，3组损伤较轻。此外，3组患者血清（白细胞介素-6 [IL-6]、肿瘤坏死因子-α和高流动性组1）和肾组织（IL-1和IL-6）炎症因子水平均明显低于2组，提示选择性给药Na2S具有有益作用。结论sna2s给药，特别是通过器官选择性给药，可能具有肾IRI后的细胞保护和抗炎作用。
BackgroundHydrogen sulfide (H2S) has recently been reported to demonstrate both antiinflammatory and cytoprotective effects; however, its efficacy has not been well documented in large animal models. In this study, we examined whether the administration of H2S offers cytoprotective effects on renal ischemia-reperfusion injury (IRI) in a preclinical miniature swine model.MethodsMajor histocompatibility complex-inbred, CLAWN miniature swine (n= 9) underwent a right nephrectomy, followed by induction of a 120-min period of warm ischemia via placement of clamps on the left renal artery and vein. Group 1 (n= 3) underwent renal ischemia without H2S administration. Groups 2 (n= 3) and 3 (n= 3) received Na2S (prodrug of H2S) 10 min before reperfusion of the ischemic kidneys followed by a 30-min of Na2S postreperfusion intravenously (group 2) or selective administration of Na2S via the left renal artery (group 3). IRI was assessed by kidney biopsies, levels of inflammatory cytokines in sera and kidney tissue.ResultsAnimals in group 1 had significantly higher serum creatinine levels compared with animals in groups 2 and 3 (P< 0.01). Histology showed severe tubular damage with TUNEL-positive cells in group 1 on postoperative day 2 compared with mild damage in group 2 and minimal damage in group 3. Furthermore, levels of inflammatory cytokines in both serum (interleukin-6 [IL-6], tumor necrosis factor-α, and high-mobility group box 1) and renal tissue (IL-1 and IL-6) in group 3 were markedly lower than in group 2, suggesting beneficial effects of selective Na2S administration.ConclusionsNa2S administration, especially via an organ selective approach, appears to potentially offer cytoprotective and antiinflammatory effects following renal IRI.