摘要
目的 探讨肠源性内毒素血症对急性坏死型胰腺炎 (ANP)的促成作用及其可能机制。方法 C5 7BL/ 6小鼠随机分成 4组 :Ⅰ组 ,急性水肿型胰腺炎 (AEP)组 (n =2 0 ) ;Ⅱ组 ,AEP +脂多糖 (LPS)处理组 (n =2 0 ) ;Ⅲ组 ,LPS组 (n =2 0 ) ;Ⅳ组 ,正常对照组 (n =5 )。腹腔内间隔 1h共 7次 ,注射 5 0 μg/kg体重雨蛙素诱导小鼠AEP。第 6小时胃管内灌入 5mg/kg体重LPS溶液。监测 12、2 4、48h和 5d血清淀粉酶、乳酸脱氢酶 (LDH)活性 ;胰组织髓过氧化物酶 (MPO)活性和组织变化 ;免疫组化观察胰组织Mac 1(CD11b/CD18)、E选择素、P选择素和细胞间黏附分子 (ICAM 1)表达 ;RT PCR和Southern印迹检测胰组织TNFα、IL 1β、IL 6和IFNγmRNA变化。 结果 雨蛙素诱导小鼠AEP。LPS单独并不引起胰组织明显病理变化和血清淀粉酶、LDH活性改变。然而 ,同剂量LPS则使小鼠AEP胰损伤加重 ,血清淀粉酶和LDH活性显著增加 ;胰组织Mac 1表达增强 ;MPO活性增加 ;E选择素、P选择素和ICAM 1表达增强 ;TNFα、IL 1β、IL 6和IFNγmRNA表达上调。 结论 肠源性内毒素血症可促使AEP转化为ANP ,黏附分子介导的中性粒细胞过度聚集和大量细胞因子释放 。
Objective To investigate the deleterious effects of enterogenous endotoxemia on the course of acute pancreatitis in mice, and its possible mechanisms. Methods Sixty five C57BL/6 mice were assigned to 4 groups randomly, including acute edematous pancreatitis (AEP), lipopolysacchride (LPS), AEP plus LPS and normal control. AEP was induced by intraperitoneal injection of cerulein with a dosage of 50 μg/kg at hourly interval for seven times under ether anesthesia. LPS was administrated via a gastric tube with a dosage of 5 mg/kg at 6 h after the first cerulein or saline injection. Serum amylase and LDH activities were measured at 12 h, 24 h, 48 h and 5 d. Pathological alteration in pancreas was studied. Expressions of Mac 1 (CD11b/CD18), P selectin, E selectin and ICAM 1 were evaluated by using inmmunohistochemical procedures. Expressions of cytokine genes were determined by means of RT PCR and Southern blot. Myeloperoxidase (MPO) activity in pancreas was also analyzed. Results Cerulein induced a typical changes of AEP in mice, which was confirmed by pathological changes and hyperamylasemia. LPS alone didn't develop either morphological changes or biochemical alterations. However, cerulein induced AEP challenged by LPS could cause marked parenchymal necrosis and hemorrhage with significant increment of serum amylase and LDH activities. Expressions of Mac 1, P selectin, E selectin and ICAM 1 in pancreas were enhanced. Cytokine genes including TNFα,IL 1β,IL 6 and IFNγ mRNA were also upregulated. MPO activity was increased. Conclusion This study suggested that enterogenous endotoxemia, which could not induce pancreatic injury per se , could induce AEP into ANP in mice. Over stimulation of neutrophils and releasing of pro inflammatory mediators might be the contributing factors.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2001年第2期71-74,共4页
Chinese Journal of Digestion
基金
德国洪堡基金会
上海市科技启明星培养计划资助项目!(99QB14 0 0 9)
