Protective Effect of Hypertonic Saline Solution on Lung Injury Induced by Intestinal Ischemia-reperfusion in Rabbits
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摘要:
目的 探讨高渗盐溶液(hypertonic saline solution, HS)对肠缺血/再灌注(intestinal ischemia-reperfusion, ⅡR)所致肺损伤的作用。 方法 72只新西兰白兔按随机数字表法分为4组(n=18):空白对照组、ⅡR组、4%HS治疗组、7.5%HS治疗组。空白对照组采用仅开腹、游离但不阻断肠系膜上动脉的假手术处理; 其余实验组采用完全夹闭肠系膜上动脉1 h后开放再灌注的方法制备ⅡR模型, 2个治疗组均在肠系膜上动脉开放前5 min输注相应浓度的氯化钠溶液。选择缺血前与再灌注后2、4、6 h 4个时间点取血测定各组肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)和白细胞介素-10(interleukin-10, IL-10)水平。再灌注后6 h每组处死8只动物, 取其肺组织测定组织中的髓过氧化物酶(myeloperoxidase, MPO)活性、肺组织湿/干比, 光镜下观察病理形态改变。 结果 ⅡR组再灌注后循环中TNF-α和IL-10水平、肺组织MPO活性、肺组织湿/干比以及病理损伤评分均较空白对照组显著升高(P < 0.05);2个HS治疗组与ⅡR组相比, 循环中TNF-α和IL-10水平、肺组织MPO活性、肺组织湿/干比以及病理损伤评分均显著下降(P < 0.05);而7.5%HS组在4%HS组基础上各指标进一步下降(P < 0.05)。 结论 HS治疗对ⅡR所致肺损伤具有保护作用, 该效应在一定范围内随着浓度的增加而增强。 Abstract:Objective To study the effect of hypertonic saline solution (HS) on lung function in intestinal ischemia-reperfusion (ⅡR) models. Methods Totally 72 rabbits were randomly divided into 4 groups (n=18):control group, ⅡR group, 4%HS group, and 7.5%HS group. The ⅡR models were produced by clamping super mesenteric artery (SMA) for 1 hour and declamping SMA for 6 hours in ⅡR group, 4%HS group, and 7.5%HS group, whereas animals in control group underwent sham operation. The corresponding sodium chloride solution was infused in the 2 treatment groups in 5 minutes before declamping SMA. Before and 2, 4, 6 hours after ⅡR, the plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were measured. At 6 hours after ⅡR, 8 rabbits in each group were killed to measure the levels of lung water and myeloperoxidase (MPO) activity in lung tissue. Meanwhile, lung morphological changes were observed under light microscope. Results The plasma TNF-α and IL-10 levels, the levels of lung water and MPO activity in lung tissue, and lung morphological score significantly increased in ⅡR group when compared with the control group(P < 0.05). Compared with the ⅡR group, the TNF-α levels in plasma, the levels of lung water and MPO activity in lung tissue, and lung morphological score in both two HS groups significantly decreased (P < 0.05), particularly in 7.5%HS group which was significantly lower than those in the 4%HS group (P < 0.05). Conclusions HS has a protective effect on the lung function during ⅡR. Such a protective effect increases along with the increase of HS concentration within certain range. -
图 1 肺组织HE染色(×100)
A.空白对照组;B.IIR组;C.4%HS治疗组;D.7.5%HS治疗组IIR、HS:同表 1
表 1 各组不同时间点循环中细胞因子改变(x ±s, n=18)
细胞因子 组别 时间点 夹闭SMA前 开放SMA后2 h 开放SMA后4 h 开放SMA后6 h TNF-α(μg/L) 空白对照组 3.55±0.49 3.65±0.51 3.78±0.52 3.72±0.59 IIR组 3.48±0.43 23.80±4.22*§ 14.22±2.69*§ 7.48±1.49*§ 4%HS治疗组 3.38±0.39 15.48±1.59*†§ 9.35±1.41*§ 6.75±0.96*§ 7.5%HS治疗组 3.55±0.52 10.32±2.11*‡§ 7.68±1.32*§ 4.23±1.00*§ IL-10(μg/L) 空白对照组 2.48±0.75 2.53±0.80 2.53±0.79 2.62±0.83 IIR组 2.56±0.67 8.90±2.75*§ 9.32±2.84*§ 9.97±3.00*§ 4%HS治疗组 2.54±0.87 12.30±1.54*†§ 13.70±1.82*†§ 11.46±1.40*†§ 7.5%HS治疗组 2.50±0.60 14.54±2.02*‡§ 16.55±1.23*‡§ 13.57±1.38*‡§ SMA:肠系膜上动脉;TNF-α:肿瘤坏死因子-α;IL-10:白细胞介素-10;IIR:肠缺血/再灌注;HS:高渗盐溶液;与空白对照组比较,*P<0.05;与IIR组比较,†P<0.05;与4%HS治疗组比较,‡P<0.05;与夹闭SMA前比较,§P<0.05 -
[1] Ding LA, Li JS. Intestinal failure:pathophysiological elements and clinical diseases[J]. World J Gastroenterol, 2004, 10:930-933. doi: 10.3748/wjg.v10.i7.930 [2] Hassoun HT, Kone BC, Mercer DW, et al. Post-injury multiple organ failure:the role of the gut[J]. Shock, 2001, 5:1210. http://www.ncbi.nlm.nih.gov/pubmed/11198350 [3] Wheeler AP, Bernard GR, Acute lung injury and the acute respiratory distress syndrome:a clinical review[J]. Lancet, 2007, 369:1553-1564. doi: 10.1016/S0140-6736(07)60604-7 [4] 徐军, 梁璐, 王仲, 等.四种溶液对失血性休克犬血流动力学的影响[J].中华急诊医学杂志, 2007, 16:21-25. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=jzyx200701006 [5] Kramer GC, Perron PR, Lindsey DC, et al. Small volume resuscitation with hypertonic saline dextran solution[J].Surgery, 1996, 100:239-244. http://www.ncbi.nlm.nih.gov/pubmed/2426818/ [6] Coimbra R, Hoyt DB, Junger WG, et al. Hypertonic saline resuscitation decreases susceptibility to sepsis following hemorrhagic shock[J]. J Trauma, 1997, 42:602-607. doi: 10.1097/00005373-199704000-00004 [7] Derks CM, Jacobovitz-Derks D. Embolic pneumopathy induced by oleic acid. A systemic morphologic study[J]. Am J Pathol, 1977, 87:143-158. http://www.europepmc.org/abstract/MED/851163 [8] Welborn MB, Oldenburg HS, Hess PJ, et al. The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair[J]. Crit Care Med, 2000, 28:3191-3197. doi: 10.1097/00003246-200009000-00013 [9] Oreopoulos GD, Wu H, Szaszi K, et al. Hypertonic preconditioning prevents hepatocellular injury following ischemia/reperfusion in mice:a role for interleukin 10[J]. Hepatology, 2004, 40:211-220. doi: 10.1002/hep.20281 [10] Powers KA, Woo J, Khadaroo KG, et al. Hypertonic resuscitation of hemorrhagic shock up-regulate the anti-inflammatory response by alveolar macrophages[J]. Surgery, 2003, 134:312-318. doi: 10.1067/msy.2003.246 [11] Attuwaybi B, Kozar RA, Gates KS, et al. Hypertonic saline prevents inflammation, injury, and impaired intestinal transit after gut ischemia/reperfusion by inducing heme oxygenase 1 enzyme[J]. J Trauma, 2004, 56:749-758. doi: 10.1097/01.TA.0000119686.33487.65 [12] 周彬, 霍正禄, 杨兴易.高渗盐羟乙基淀粉液对失血性休克犬中性粒细胞Fas表达的影响[J].中华急诊医学杂志, 2007, 16:21-25. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=jzyx200601008 [13] Murao Y, Loomis W, Wolf P, et al. Effect of dose of hypertonic saline on its potential to prevent lung tissue damage in a mouse model of hemorrhagic shock[J]. Shock, 2003, 20:29-34. doi: 10.1097/01.shk.0000071060.78689.f1 [14] Gonzalez EA, Kozar RA, Suliburk JW, et al. Conventional dose hypertonic saline provides optimal gut protection and limits remote organ injury after gut ischemia reperfusion[J]. J Trauma, 2006, 61:66-73. doi: 10.1097/01.ta.0000224190.65542.e2