灯盏花注射液通过抑制减IκB-α/NF-κB/ICAM-1通路轻大鼠肠缺血再灌注损伤

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目的探讨灯盏花注射液在肠缺血再灌注早期小肠损伤中的作用及其机制。方法 48只8周龄健康雄性SD大鼠随机分为假手术对照(Sham)组,肠I/R损伤(IIR)组,灯盏花注射液处理组(EB+IIR)组,IκB-α抑制剂TPCA-1处理(TP+IIR)组。EB+IIR组在术前7 d每天经腹腔注射给予灯盏花注射液20 mg(/kg·d),TP+IIR组在术前30 min尾静脉给予TPCA-1(12 mg/kg),另两组注入等量生理盐水。采用夹闭SD大鼠肠系膜前动脉45 min后再灌注6h的方法造成肠缺血再灌注损伤模型。处死大鼠取小肠标本,HE染色观察肠组织病理学改变,ELISA检测肠粘膜组织TNF-α、IL-1β和IL-6水平;蛋白印迹法检测肠粘膜组织IκB-α、NF-κB、ICAM-1蛋白表达水平。结果肠缺血再灌注导致明显小肠损伤,肠组织炎症指标明显增高,表现为TNF-α、IL-1β和IL-6含量明显升高(与假手术组比较P<0.05),IκB-α/NF-κB/ICAM-1通路活化;灯盏花注射液预处理可抑制小肠组织IκB-α/NF-κB/ICAM-1活化,减轻小肠缺血再灌注引起的早期肠道损伤,并下调小肠组织TNF-α、IL-1β和IL-6含量(与缺血再灌注组比较P<0.05),同样,应用IκB-α磷酸化抑制剂TPCA-1处理后,IκB-α/NF-κB/ICAM-1通路受到抑制,小肠损伤程度得到减轻。结论灯盏花注射液预处理通过抑制IκB-α/NF-κB/ICAM-1通路减轻大鼠肠缺血再灌注损伤。 Objective To investigate the effect and mechanism of Breviscapine Injection on small intestine injury induced by intestinal ischemia-reperfusion. Methods Forty 8-week-old healthy male Sprague-Dawley rats were randomly divided into three groups: sham operation group, intestinal I / R injury (IIR) group, erigeron injection treatment group (EB + IIR) TPCA-1 treated (TP + IIR) group. EB + IIR group was injected with Erigeron Breviscapine Injection 20 mg / kg · d daily for 7 d before operation. TPCA-1 (12 mg / kg) was given to tail vein in TP + IIR group 30 min before operation. Two groups were injected with the same amount of saline. The occlusion of anterior mesenteric artery of SD rats for 45 min followed by 6 h of reperfusion resulted in a model of intestinal ischemia-reperfusion injury. The rats were sacrificed and the small intestine specimens were obtained. The pathological changes of intestinal tissue were observed by HE staining. The levels of TNF-α, IL-1β and IL-6 in intestinal mucosa were detected by ELISA. The expressions of IκB-α, NF- -1 protein expression level. Results Intestinal ischemia-reperfusion resulted in obvious intestinal damage and inflammation of intestinal tissue. The contents of TNF-α, IL-1β and IL-6 were significantly increased (P <0.05 compared with sham operation group) Activation of NF-κB / ICAM-1 pathway was inhibited by pre-treatment of Erigeron Breviscapus injection, which could inhibit the activation of IκB-α / NF-κB / ICAM-1 in small intestine and alleviate the early intestinal damage induced by intestinal ischemia reperfusion. The levels of TNF-α, IL-1β and IL-6 in ischemic group were significantly higher than those in ischemia-reperfusion group (P <0.05). Similarly, IκB-α / NF-κB / ICAM -1 pathway was inhibited, the degree of lesion was reduced. Conclusion Breviscapine injection preconditioned to relieve intestinal ischemia-reperfusion injury in rats by inhibiting IκB-α / NF-κB / ICAM-1 pathway.
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