Zhao Zhi-cheng, Zheng Shu-sen, Cheng Wen-liang, Wang Xuan, Qi Ying
Dept. of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China.
J Zhejiang Univ Sci. 2004 Apr;5(4):477-82. doi: 10.1631/jzus.2004.0477.
To explore the characteristics of NF-KappaB activation in the progress of pancreatitis, the relationship with expression of TNF-alpha in the inflammatory reaction, and prevent the exacerbation of pancreatitis by using NAC.
Forty-eight rats were divided into three groups: therapy (group C), pancreatitis (group B) and control (group A). NAC served as the inhibitor of NF-KappaB activation. In the time intervals of 1.5, 3.0, 6.0, 12.0 hour, NF-KappaB activation was detected with flow cytometry (FCM) and the expression of TNF-alpha mRNA and protein with in situ hybridization (ISH) and enzyme-linked immuno-sorbent assay (ELISA) respectively. Meanwhile, the level of lipase and amylase in the serum was assayed and the pathological change was evaluated.
NF-KappaB activation in the pancreatitis group was higher than that in the control group (P<0.01), peaked at 3 hours, and was depressed by the inhibitor of NF-KappaB, NAC. The expression of TNF-alpha as well as the level of lipase and amylase in the serum also rose synchronously with activation of NF-KappaB. In contrast to group A, it was significantly different (P<0.01) in group B. After using NAC in group C, all of these values were decreased and the inflammatory reaction in the pancreas abated evidently. The pathology changes of the pancreas were shown to be alleviated in group C.
First, NF-KappaB activity is intensively initiated in the course of pancreatitis and shown to have closely relationship with the release of cytokines. Second, use of NAC markedly depressed NF-KappaB activation. TNF-alpha expression is down regulated by cytokines. It is suggested that NAC probably acts as a useful agent for treatment of pancreatitis by indirectly inhibiting activation of NF-KappaB.
探讨胰腺炎进展过程中核因子-κB（NF-κB）激活的特征、其在炎症反应中与肿瘤坏死因子-α（TNF-α）表达的关系，并通过使用N-乙酰半胱氨酸（NAC）预防胰腺炎的恶化。
48只大鼠分为三组：治疗组（C组）、胰腺炎组（B组）和对照组（A组）。NAC作为NF-κB激活的抑制剂。在1.5、3.0、6.0、12.0小时的时间间隔，分别用流式细胞术（FCM）检测NF-κB激活情况，用原位杂交（ISH）和酶联免疫吸附测定（ELISA）检测TNF-α mRNA和蛋白的表达。同时，测定血清中脂肪酶和淀粉酶水平并评估病理变化。
胰腺炎组NF-κB激活高于对照组（P<0.01），在3小时达到峰值，并被NF-κB抑制剂NAC抑制。TNF-α的表达以及血清中脂肪酶和淀粉酶水平也与NF-κB激活同步升高。与A组相比，B组有显著差异（P<0.01）。C组使用NAC后，所有这些值均降低，胰腺炎症反应明显减轻。C组胰腺病理变化显示减轻。
第一，NF-κB活性在胰腺炎过程中强烈启动，且与细胞因子释放密切相关。第二，使用NAC明显抑制NF-κB激活。细胞因子下调TNF-α表达。提示NAC可能通过间接抑制NF-κB激活而成为治疗胰腺炎的有效药物。
