国际麻醉学与复苏杂志   2014, Issue (11): 2-2
    
8%乳化异氟醚预处理对缺血/再灌注损伤大鼠肾脏氧化应激反应的影响
覃兆军, 吕恩, 占乐云, 江建立, 张敏1()
1.三峡大学人民医院 宜昌市第一人民医院麻醉科
Effect of 8% emulsified isoflurane on oxidative stress in ischemia reperfusion injury rat's kidney
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摘要:

目的 观察8%乳化异氟醚(emulsified isoflurane, EI)预处理对缺血/再灌注损伤(ischemia/reperfusion injury, I/RI)大鼠肾脏氧化应激反应的影响。 方法 健康雄性SD大鼠32只,右肾切除后采用随机数字表法随机分为4组:(1)假手术(Sham)组:仅分离左侧肾蒂,不阻断肾血流;(2)肾脏I/RI组:夹闭左侧肾蒂45 min后恢复再灌注;(3)EI预处理组和(4)脂肪乳剂(lipid emulsion, LE)预处理组:分别静脉泵注8%EI、30%LE 4 ml·kg-1·h-1 30 min,停药15 min后夹闭左侧肾蒂,余同I/RI组。于肾脏再灌注3 h时采集腹主动脉血测血清肌酐(creatinine, Cr)、尿素氮(blood urea nitrogen, BUN);取肾组织测超氧化物歧化酶活性及丙二醛(malondialdehyde, MDA)含量,光镜下观察肾脏病理学变化,并行肾小管Paller评分。 结果 各组大鼠血清Cr、BUN水平、肾组织MDA含量及肾小管Paller评分:I/RI组[Cr(98±7) μmol/L, BUN(14.5±4.7) mmol/L, MDA(2.05±0.31) nmol/mg, Paller(33.5±5.6)]、EI组[Cr(62±6) μmol/L, BUN(9.3±2.3) mmol/L, MDA(1.61±0.28) nmol/mg, Paller(18.5±4.5)]、LE组[Cr(94±15) μmol/L, BUN(13.9±4.5) mmol/L, MDA(1.91±0.35) nmol/mg, Paller (32.2±3.8)]与Sham组[Cr(24±6) μmol/L, BUN(6.5±1.6) mmol/L, MDA(1.32±0.19) nmol/mg, Paller (1.6±0.9)]比较,显著升高(P < 0.05);肾组织超氧化物歧化酶活性:I/RI组[(78±12)U/mg]、EI组[(97±7)U/mg]、LE组[(79±13)U/mg]与Sham组[(117±10)U/mg]比较,显著降低(P < 0.05);分别与I/RI组和LE组相比,EI组血清Cr、BUN水平、肾组织MDA含量及肾小管Paller评分均降低(P < 0.05),肾组织超氧化物歧化酶活性均升高(P < 0.05)。I/RI组和LE组上述各指标相比差异无统计学意义(P > 0.05)。I/RI组和LE组肾组织病理学损伤最严重,EI组肾组织病理学损伤明显减轻。 结论 8%EI预处理可通过抑制肾组织氧化应激反应减轻大鼠肾脏I/RI。

关键词: 异氟醚;缺血预处理;再灌注损伤;肾;脂肪乳剂
Abstract:

Objective To observe the effect of 8% emulsified isoflurane (EI) preconditioning on oxidative stress in ischemia reperfusion injury (I/RI) rat’s kidney. Methods Thirty-two healthy male Sprague-Dawley rats were randomly divided into 4 groups after right nephrectomy: (1) sham operation (Sham) group: the left renal pedicle was not clamped; (2) I/RI group: renal I/RI was induced by occlusion of left renal pedicle for 45 min with atraumatic microclips followed by 3 h reperfusion; (3) EI group and (4) lipid emulsion (LE) group: 8% EI or 30% LE 4 ml·kg-1·h-1 was infused intravenously for 30 min respectively, then infusion was discontinued for 15 min, and renal I/RI was induced. Arterial blood samples were taken at 3 h of reperfusion to determine the concentrations of Cr and BUN. The rats were then sacrificed and the left kidneys were removed. Renal tissue superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected. The another half renal tissue, stained with hematoxylin-eosin, for optical microscopic examination and assessment of necrotic injury of the proximal tubules. Results Compared with Sham group [Cr(24±6) μmol/L, BUN(6.5±1.6) mmol/L, SOD(117±10) U/mg, MDA(1.32±0.19) nmol/mg, Paller scores (1.6±0.9)], the serum Cr and BUN, and the content of MDA and the Paller scores were obviously higher, and the activity of SOD was lower in I/RI, EI and LE group(P < 0.05)[Cr: I/RI group(98±7) μmol/L, EI group(62±6) μmol/L, LE group(94±15) μmol/L; BUN: I/RI group(14.5±4.7) mmol/L, EI(9.3±2.3) mmol/L, LE group(13.9±4.5) mmol/L; SOD: I/RI group(78±12) U/mg, EI group(97±7) U/mg, LE group(79±13) U/mg; MDA: I/RI group(2.05±0.31) nmol/mg, EI group(1.61±0.28) nmol/mg, LE group(1.91±0.35) nmol/mg; Paller scores: I/RI group (33.5±5.6), EI group (18.5±4.5), LE group (32.2±3.8)]. The serum Cr and BUN, and the content of MDA and the Paller scores were significantly decreased, while the activity of SOD was significantly increased in EI group compared with I/RI and LE group, respectively (P < 0.05). There was no significant difference in the above observational parameters between I/RI and LE group (P > 0.05). Pathological damage of renal tissue in EI group was less serious than in I/RI and LE group. Conclusion Preconditioning with 8% emulsified isoflurane can attenuate renal I/RI through inhibiting oxidative stress response in rats.

Key words: Isoflurane; Ischemic preconditioning; Reperfusion injury; Kidney; Fat emulsions