南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (08): 1146-.

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硫氢化钠防治截肢术后大鼠肾脏损伤的机制

张颖,刘宁,任青爱,张海峰,谢晓华   

  • 出版日期:2013-08-20 发布日期:2013-08-20

Sodium hydrosulfide for prevention of kidney damage in rats after amputation

  • Online:2013-08-20 Published:2013-08-20

摘要: 目的探讨截肢术后大鼠肾脏损伤的机制,探索外源性硫化氢(H2S)供体硫氢化钠(NaHS)的应用对肾脏结构和功能的影
响,并了解硫化氢在防治肾脏损伤中的作用机制。方法实验分为两部分。第1部分:将雄性Wistar大鼠按手术时间随机分为正
常对照、手术后6 h、NaHS干预、炔丙基甘氨酸(PPG)干预组,每组7只。测定血浆H2S、肾组织肾损伤分子-1(KIM-1)、髓过氧化
物酶(MPO)、丙二醛(MDA)、一氧化氮、尿素氮、肌酐浓度和肾组织胱硫醚β-裂解酶(CSE)活性、MPO、MDA、KIM-1水平;光镜
观察肾组织形态学变化,电镜观察线粒体结构变化。第2部分:将雄性SD大鼠随机分为4组,每组大鼠8只。提取各组肾线粒
体后测定呼吸控制率、膜电位及ATP酶活性。结果截肢后6 h 大鼠肾脏细胞和线粒体结构出现了损伤性变化,血浆及肾脏
KIM-1含量明显增加(P<0.01),而H2S/CSE水平明显下降(P<0.01),NaHS干预后血浆H2S/肾脏CSE水平明显升高(P<0.01),而
肾组织损伤减轻,血浆及肾脏KIM-1含量明显降低(P<0.01)。与正常对照组相比,手术后大鼠肾脏线粒体呼吸控制率、膜电位
及ATP酶活性显著降低(P<0.01),应用NaHS后以上指标出现明显升高,而应用PPG后无明显改善。结论截肢创伤可导致大鼠
肾脏结构和功能的损害,并导致线粒体的损伤,H2S供体NaHS的应用可使线粒体功能明显改善,并进一步减轻肾脏结构和功能
的损害,表明H2S作为是一种新的内源性介质,可能通过多条途径作用于线粒体,调节能量代谢途径,参与组织了损伤与修复的
一系列病理生理过程。

Abstract: Objective To explore the mechanism of kidney injury in rats following amputation and the protective effects of
sodium hydrosulfide (NaHS) on kidney structure and function. Methods Male Wistar rats were randomly divided into normal
control, 6 h after operation, NaHS intervention, and propargyl glycine (PPG) intervention groups (n=7). Plasma level of H2S,
kidney injury molecule-1 (KIM-1), myeloperoxidase enzyme (MPO), malondialdehyde (MDA), nitric oxide (NO), urea
nitrogen, creatinine, and renal tissue MPO, MDA, and KIM-1 levels, and activity of CSE were measured and the renal
histological and mitochondrial structural changes were observed using optical and electron microscopy. In another experiment
with SD rats, the rats were randomized also into these 4 groups (n=8) for measurement of renal mitochondrial respiratory
control ratio, membrane potential and ATP activity. Results Traumatic changes in rat kidney cells and mitochondrial structure
occurred in the rats 6 h after amputation with significantly increased plasma and renal KIM-1 (P<0.01) but significantly
decreased H2S/CSE levels (P<0.01). Plasma H2S/kidney CSE level was significantly increased following NaHS intervention (P<
0.01), which reduce the damage of the kidney tissue and significantly lower plasma and renal KIM-1, NO, BUN, Cr, MPO, and
MDA (P<0.01). Rat kidney mitochondrial respiratory control ratio, membrane potential and ATP activity all decreased
significantly after amputation (P<0.01) increased significantly after the application of NaHS; such improvements did not occur
following PPG treatment. Conclusion Amputation can lead to damage to the structure and function of the rat kidneys, and
NaHS can significantly improve mitochondrial function and further reduce renal structural and functional impairments,
suggesting that H2S, as an endogenous mediator, may act on the mitochondria through several pathways to regulate energy
metabolism and participate in the pathophysiological processes of tissue damage and repair.