大黄对大鼠肠缺血再灌注所致肺损伤的作用

背景:肠道因素尤其是肠缺血再灌注可导致远隔器官损伤是创伤。中药大黄能通过清除氧自由基,促进肠粘膜内杯状细胞增生,抑制肠道内细菌过度繁殖和肠道内毒素吸收及活血化瘀、改善微循环等途径发挥良好的肠黏膜屏障保护作用,进而可能发挥防治肺损伤的作用。目的:观察大黄对肠缺血-再灌注所致肺损伤的防治效应,以及对肿瘤坏死因子和磷脂酶A2的影响。设计:随机对照观察。单位:解放军兰州军区乌鲁木齐总医院急诊科。材料:实验于2003-02/07在解放军第二军医大学完成。选取SD大鼠80只,随机分为肠缺血再灌注组24只,假手术组16只,治疗组24只,生理盐水组16只四组。方法:肠缺血-再灌注组,术前禁食,麻醉,然后经腹正中切口,分离肠系膜上动脉,无创血管夹夹闭之,缝合切口;45min后取出动物夹,恢复血供。治疗组造模同肠缺血再灌注组,恢复血供前30min经胃管灌入精黄片600mg/kg混悬液,。生理盐水组造模同肠缺血再灌注组,于恢复血供前30min经胃管灌入等量的生理盐水。假手术组除不夹闭肠系膜上动脉外,其余手术过程均同肠缺血-再灌注组。以病理学改变及125Ⅰ标记牛血清白蛋白肺摄取指数作为评价肺损伤的指标,分别测定各组动物不同时间肺组织TNF含量及血清、肺及小肠组织PLA2活性。主要观察指标:观察125Ⅰ标记牛血清白蛋白肺摄取指数,血浆、肺组织肿瘤坏死因子含量,血清、肺及小肠组织磷脂酶A2活性。结果:①肺组织病理形态学变化:假手术组未见明显异常;肠缺血再灌注组6h后肺间质出现水肿,并有中性粒细胞浸润,可见肺泡水肿,有少量出血及纤维蛋白渗出。治疗组仅见轻度肺间质水肿及少量中性粒细胞。②肺组织超微病理变化:假手术组未见明显变化。肠缺血再灌注组6h后,可见肺毛细血管内皮细胞肿胀,中性粒细胞向肺间质及肺泡腔渗出。治疗组无上述变化。③肺组织肿瘤坏死因子变化:假手术组和治疗组(再灌注组30min)明显低于肠缺血再灌注组(再灌注30min)(0.235±0.114,1.374±0.550,16.315±4.587,P<0.01)。④125Ⅰ-BSA肺摄取指数:治疗组明显低于肠缺血-再灌注组和生理盐水组(P<0.01),与假手术组差异无显著性(P>0.05)。结论:早期应用大黄有助于防治肠源性肺损伤的发生。进而发挥组织病程向多器官功能不全综合征发展的重要作用,这种作用可能是通过抑制TNF和PLA2等介质的释放实现的。

Effect of rhubarb on pulmonary injury of rats induced by intestinal ischemia-reperfusion

BACKGROUND: Intestinal tract factors, especially intestinal ischemiareperfusion, can induce the injury of remote organ. Chinese herb, rhubarb,can clear oxygen free radical to promote the proliferation of beaker cell in intestinal mucous membrane, inhibit excessive multiplication of bacterium and endotoxin absorption in the intestinal tract, activate blood circulation and remove blood stasis, improve microcirculation and other ways to protect intestinal mucous membrane barrier, so as to prevent and treat pulmonary injury.OBJECTIVE: To observe the preventing and treating effect of rhubarb on intestinal ischemia/reperfusion-induced pulmonary injury and the effect of rhubarb on tumor necrosis factor and phospholipase A2 (PLA2).DESIGN: A randomized controlled observation.SETTING: Department of Emergency, Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA.MATERIALS: This experiment was carried out in the Second Military Medical University of Chinese PLA from February to July 2003. Totally 80SD rats were selected and randomly divided into intestinal ischemia/reperfusion group (n=24), sham operation group (n=46), treatment group (n=24) and normal saline group (n=16).METHODS: In the intestinal ischemia-reperfusion group, rats were fasted before operation. They were anesthetized and given a median abdominal incision. Superior mesenteric artery was isolated and occluded by vascular clamp without wound, and then the incision was sutured; 45 minutes later,vascular clamp was taken out to recover blood supply. For the treatment group, modeling was the same as that in the intestinal ischemia/reperfusion group, 600 mg/kg suspension of rhubarb extract was gastrointestinally perfused into the rats 30 minutes before recovering blood supply. For the normal saline group, modeling was the same as that in the intestinal ischemia/reperfusion group; same dosage of normal saline was gastrointestinally perfused into the rats 30 minutes before recovering blood supply. For the sham operation group, occlusion of superior mesenteric artery was omitted. Taking pathological change and 125I-labeled bovine serum albumin pulmonary uptake index as the index to evaluate pulmonary injury, TNF content and serum of pulmonary tissue and PLA2 activity of lung and intestinal tissue of animals in each group were measured respectively at different time points.MAIN OUTCOME MEASURES: 125I labeled bovine bovine serum albumin uptake index, tumor necrosis factor content of blood and pulmonary tissue, and PLA2 activity of serum, lung and intestinal tissue RESULTS: ① Pathological and morphological change of pulmonary tissue: There was no obvious abnormality in the sham operation group; In the intestinal ischemia-reperfusion group, 6 hours later, pulmonary interstitial edema, neutrophile infiltration appeared and alveolar edema was also found, and there were a little haemorrhage and exudation of fibrin. Only mild pulmonary interstitial edema and a small quantity of neutrophiles were found in the treatment group. ② Ultramicro-pathological change of pulmonary tissue: There was no obvious change in the sham operation group. In the intestinal ishcemia/reperfusion group, 6 hours later, pulmonary capillary endothelial cells were swelled and neutrophilic granulocyte leaked into pulmonary stroma and alveolar space. There were no above changes in the treatment group. ③ Change of tumor necrosis factor of pulmonary tissue in the sham operation group or treatment group (reperfusion for 30 minutes) was significantly lower than that in the intestinal ischemiareperfusion group (reperfusion for 30 minutes) (0.235±0.114,1.374±0.550,16.315±4.587,P ＜ 0.01). ④125I-BSA pulmonary uptake index in the treatment group was significantly lower than that in the intestinal ischemiareperfusion group and normal saline group (P ＜ 0.01), without significant difference in comparison with sham operation group (P ＞ 0.05).CONCLUSION: Early application of rhubarb is helpful to prevent and treat lung injury following small intestine ischemic reperfusion, so as to inhibit tissue disease course to deve1op multiple organ dysfunction syndrome,which might be implemented through inhibiting the release of TNF and PLA2 and other media.