Goksin Ibrahim, Adali Fahri, Enli Yasar, Akbulut Metin, Teke Zafer, Sackan Gokhan, Ocak Erkin, Ozcan Ali Vefa
Department of Cardiovascular Surgery, School of Medicine, Pamukkale University, Denizli, Turkey.
Ann Vasc Surg. 2011 Nov;25(8):1118-28. doi: 10.1016/j.avsg.2011.07.007.
Abdominal aortic surgery can cause ischemic/reperfusion (I/R) injury not only in the lower limbs but also in remote organs such as kidneys. Venous blood volume exclusion from the inferior vena cava (phlebotomy) or/and mannitol are used as a treatment for I/R injury of kidney in humans, despite the fact that the effectiveness of these treatments is still debated. The aim of this study was to evaluate the effects of phlebotomy or/and mannitol on rat kidneys in a model of lower limbs I/R-induced acute renal injury (ARI).
Thirty male Wistar albino rats were used and divided into five groups: (I) sham-operated group, laparotomy without I/R injury (group [S], n = 6); (II) I/R group, infrarenal aortic cross-clamp was used for lower limbs I/R, 3 hours of ischemia followed by 2 hours of reperfusion (group [I/R], n = 6); (III) I/R + phlebotomy group, identical to group [I/R] except for 1 mL of blood aspiration from the inferior caval vein just after ischemia (group [P], n = 6); (IV) I/R + mannitol-treated group, these rats were subjected to I/R and received a bolus injection of mannitol (group [M], n = 6); and (V) I/R + phlebotomy + mannitol-treated group (group [P + M], n = 6), the same procedures were performed as those described for previous groups. At the end of 2-hour reperfusion, all rats were sacrificed. Both kidneys were harvested for biochemical assay (myeloperoxidase [MPO] and superoxide dismutase [SOD] activities, and malondialdehyde [MDA] and reduced glutathione levels) and for histopathological examination (tubular necrosis and acute inflammation on kidney [ARI score]).
Aortic I/R significantly increased the level of MDA (reflecting lipid peroxidation), SOD (enzymatic endogenous antioxidant), and MPO (reflecting neutrophil infiltration) activity (p < 0.05). Phlebotomy or/and mannitol treatments significantly decreased the level of MDA, SOD, and MPO activity and increased glutathione level (nonenzymatic antioxidant in the kidney tissues) (p < 0.05). Histological evaluation of ARI score showed that aortic I/R significantly increased (p value for group [S] versus group [I/R] was 0.012), whereas phlebotomy or/and mannitol treatments significantly decreased tubular necrosis and inflammatory infiltration (p values for group [I/R] versus group [P], [M], and [P + M] were 0.043, 0.043, and 0.003, respectively).
This experiment clearly indicated that the lower limbs I/R-induced ARI attenuated significantly by phlebotomy or/and mannitol treatments. Phlebotomy plus mannitol is more effective treatment than phlebotomy or mannitol alone in preventing lower limbs I/R-induced ARI in rats. Further clinical studies are required to clarify whether phlebotomy or/and mannitol treatments are beneficial in alleviating of ARI during abdominal aortic surgery.
腹主动脉手术不仅会导致下肢缺血/再灌注（I/R）损伤，还会对肾脏等远处器官造成损伤。尽管下腔静脉放血（静脉切开术）或/和甘露醇作为治疗人类肾脏I/R损伤的方法，其有效性仍存在争议，但仍被应用。本研究的目的是评估在下肢I/R诱导的急性肾损伤（ARI）模型中，静脉切开术或/和甘露醇对大鼠肾脏的影响。
使用30只雄性Wistar白化大鼠，分为五组：（I）假手术组，仅行剖腹术，无I/R损伤（[S]组，n = 6）；（II）I/R组，使用肾下腹主动脉交叉夹闭造成下肢I/R，缺血3小时，再灌注2小时（[I/R]组，n = 6）；（III）I/R + 静脉切开术组，除在缺血后立即从下腔静脉抽取1 mL血液外，其余与[I/R]组相同（[P]组，n = 6）；（IV）I/R + 甘露醇治疗组，这些大鼠接受I/R并给予一次大剂量甘露醇注射（[M]组，n = 6）；（V）I/R + 静脉切开术 + 甘露醇治疗组（[P + M]组，n = 6），进行与前几组相同的操作。在2小时再灌注结束时，处死所有大鼠。摘取双侧肾脏进行生化检测（髓过氧化物酶[MPO]和超氧化物歧化酶[SOD]活性，以及丙二醛[MDA]和还原型谷胱甘肽水平）和组织病理学检查（肾小管坏死和肾脏急性炎症[ARI评分]）。
主动脉I/R显著增加了MDA水平（反映脂质过氧化）、SOD（内源性酶抗氧化剂）和MPO活性（反映中性粒细胞浸润）（p < 0.05）。静脉切开术或/和甘露醇治疗显著降低了MDA、SOD和MPO活性水平，并增加了谷胱甘肽水平（肾脏组织中的非酶抗氧化剂）（p < 0.05）。ARI评分的组织学评估显示，主动脉I/R显著增加（[S]组与[I/R]组的p值为0.012），而静脉切开术或/和甘露醇治疗显著减少了肾小管坏死和炎症浸润（[I/R]组与[P]组、[M]组和[P + M]组的p值分别为0.043、0.043和0.003）。
本实验清楚地表明，静脉切开术或/和甘露醇治疗可显著减轻下肢I/R诱导的ARI。在预防大鼠下肢I/R诱导的ARI方面，静脉切开术加甘露醇比单独使用静脉切开术或甘露醇更有效。需要进一步的临床研究来阐明静脉切开术或/和甘露醇治疗在减轻腹主动脉手术期间的ARI方面是否有益。
