草木犀流浸液片对脓毒症大鼠肺组织VEGF及肺血管通透性的影响

Effects of melilotus extrac on lung tissue VEGF and pulmonary vascular permeability in sepsis rats

探讨草木犀流浸液片对盲肠结扎穿孔术(CLP)脓毒症大鼠肺VEGF及肺血管通透性的影响。将80只雄性SD大鼠随机分为四组:①正常对照组20只;②假手术组20只;③对照组20只;④治疗组20只。假手术组只开腹,不行CLP;对照组和治疗组建立CLP脓毒症模型。术前2h治疗组给予草木犀流浸液片20mg/kg,每8h一次,24h处死各组大鼠大鼠,观察肺组织VEGF mRNA、NF-κB mRNA、NF-κB p65及血清VEGF-a、TNF-α、IL-6、IL-1β、IL-8、IFN-γ、IL-10、IL-12的变化;同时测定肺组织通透性(EB)、湿/干重比(W/D)及肺组织病理变化。研究发现:与正常对照组比较,VEGFmRNA、NF-κB p65mRNA、NF-κB p65、VEGF、TNF-α、IL-6、IL-1β、IL-8、IFN-γ、IL-10、IL-12在假手术者无明显变化,差异无统计学意义P>0.05;对照组、治疗组显著升高,差异有非常显著意义P<0.01;与对照组比较,治疗组VEGF mRNA、NF-κB p65mRNA、NF-κB p65、VEGF、TNF-α、IL-6、IL-1β、IL-8显著降低,IFN-γ、IL-10、IL-12显著升高,差异有统计学意义P<0.05。VEGF mRNA与NF-κB mRNA、VEGF与NF-κB p65分别具有正相关性(r=0.852,P<0.05;r=0.794,P<0.05)。病检也发现,治疗组肺病病理损伤较对照组明显减轻。结果提示:草木犀流浸液片能够抑制CLP脓毒症大鼠肺组织NF-κB mRNA、VEGF mRNA的表达,降低血清VEGF、TNF-α、IL-6、IL-1β、IL-8水平,促进IFN-γ、IL-10、IL-12的产生,显著降低脓毒症大鼠肺组织微血管通透性,对脓毒症大鼠肺组织具有保护作用。

To observe the effects of melilotus extract on lung tissue VEGF and pulmonary vascular permeability in sepsis rats, eighty male SD rats weighing 280-300 g at specific pathogen free （SPF） level were randomly divided into four groups, which were control group, sham operation group, sepsis group and treatment group, and every group containing 20 rats. Sepsis mod- el of rats were established by the operation of caecal ligation and puncture. After half an hour of operation, treatment group was administered with melilotus extract 20mg/kg every 8h imtramuscularly, whereas normal control group and control group were given equivalent volume normal saline until 24 hours observation ended, and executed rats. Observe the expression of VEGF mRNA, the nf-kappa activity in the lung tissue, and VEGF, TNF-α, 1L-6, IL-1β, IL-8, IFN-7, IL-10, IL-12 in palsma, lung tissue （EB） permeability, wet/dry weight ratio （W/D） and lung tissue pathology were detected. The result found that in comparing with control group, the expression of VEGF mRNA, the NF-κB p65mRNA, NF-κB p65, VEGF, TNF-α, IL-6, IL-1β, IL-8 significantly reduced, IFN-γ, IL-10, IL-12 significantly increased in treatment group P〈0. 05. VEGF mRNA and the NF-κB mRNA, VEGF and the NF-κB p65 were positive correlation （r=0. 852, P〈0.05; r=0. 794, P〈0.05）. HE-stained section found that lung pathological damage in the treatment group significantly lighter than that of control group, The result suggested that melilotus extract can inhibit the NF-κB activity, and restrain the expression of VEGF mRNA in the lung tissue, reduce TNF-α, IL-6 level in serum; significantly reduce microvascular permeability and wet/dry weight ratio in lung tissue. It is a reliable protection agent for septic rats to induce acute lung injury, and its mechanism of action may be involved in the inhibition expression of VEGF in CLP sepsis rat.