摘要
目的通过研究丙谷胺早期干预对SAP发生发展过程中胰腺组织结构,炎症介质的影响,探讨丙谷胺对SAP的作用机制以及各炎症介质间的相互关系。方法将54只SD大鼠分为假手术组,SAP组和丙谷胺干预组,每组谷18只,采用胰管逆行注射5%牛磺胆酸钠制成大鼠SAP模型,分别于术后6、12和24h抽血,用自动生化分析仪检测血液中淀粉酶的含量;凝胶电泳迁移率法检测外周血单核细胞核转录因子-κB(NF-κB)的活性;ELISA法检测血液中IL-1β及TNF-α的水平;半定量RT-PCR检测血液中IL-1β及TNF-α mRNA表达以及胰腺的病理变化。结果假手术组胰腺未见明显病理改变,SAP组各时点见胰腺组织明显水肿、出血和坏死,且随着时间的延长,病变逐渐加重;丙谷胺干预组胰腺水肿、出血、坏死及炎性细胞浸润仍较明显,但在各时间点均较SAP组显著减轻(P<0.01)。丙谷胺组NF-κB活性在6、12和24h都显著低于SAP组(P<0.05)。SAP组大鼠血清AMY、IL-1β、TNF-α的含量及IL-1β、TNF-α mRNA转录水平在造模后6h均开始不断升高,于24h达峰值;丙谷胺组以上各项指标也逐渐升高,但与SAP组比较,在各时间点都显著降低(P<0.05)。结论CCK受体拮抗剂丙谷胺可能通过炎症介质的信息传导通路,从源头上抑制NF-κB的激活,从而进一步影响细胞因子和炎症介质的释放,缩小SAP时细胞因子的级联效应,达到改善SAP预后的目的。
[Objective] To investigate the effects of early using proglumide to pancreatic tissues and mediators of inflammation in severe acute pancrititis（SAP）, and to discuss the effect mechanism of early using proglumide to SAP and relation of mediators of inflammation. [Methods] Rat SAP model was built by retrograde injecting of 5% sodium taurocholate into the pancreatic duct. 54 rats were randomly divided into 3 groups, named sham operation group, SAP group and early using proglumide group. Serum levels of AMS, IL-1β, TNF-α, the activity of NF-κB, the expression of IL-1β, TNF-α mRNA at the 6, 12 and 24 hour time points were measured. [Results] Any pathological changes were not found in sham operation group; inflammatory changes including the tissue oedema, hemorrhage, necrosis and inflammatory cell infiltration were obvious in early using proglumide group, but decreased significantly when contrast with SAP group, the serum levels of AMS, IL-1β, TNF-α, the activity of NF-κB, the expression of IL-1β, TNF-α mRNA were significantly lower than those in SAP group at each time point. [Conclusion] Proglumide maybe affect the releasing of cell factor and mediators of inflammation by inhibiting the activation of NF-κB from source beginning, minificate the cascade effect of cell factor in SAP, and improve the prognosis of SAP.
出处
《中国医学工程》
2007年第1期9-11,15,共4页
China Medical Engineering
