摘要
目的 :观察氨甲喋呤 (MTX)对急性胰腺炎时炎症性细胞因子和抗炎症细胞因子的调节作用 ,探讨氨甲喋呤治疗急性胰腺炎的作用机制。方法 :实验用雄性 SD大鼠随机分为 3组 :1正常对照组 (6只 ) ;2胰腺炎组 (8只 ) :采用开腹胰管注射质量分数为 5 %的牛磺胆酸钠 (1.0 m l/ kg)制备急性胰腺炎模型 ;3氨甲喋呤组(6只 ) :胰腺炎诱导成功后 0 .5小时静注氨甲喋呤 (1.2 m g/ kg)。制模后 2、6和 2 4小时处死动物 ,分别取血查肿瘤坏死因子α(TNFα)、白介素 1(IL 1)、IL 6、IL 10和转移生长因子β(TGFβ)及胰淀粉酶、胰腺湿重、白细胞计数。结果 :急性胰腺炎时血中炎症细胞因子和抗炎症细胞因子均显著升高 ;使用氨甲喋呤治疗后 ,上述细胞因子均下降 ,其中 TNFα、IL 1和 IL 6在 2、6、2 4小时均明显下降 (P均 <0 .0 5 ) ,IL 10和TGFβ在 2 4小时均下降明显 (P均 <0 .0 5 ) ;制模后 2 4小时大鼠胰腺湿重〔(1.5 3± 0 .13) g〕和血淀粉酶含量〔(1817.2 5± 4 5 9.35 ) U/ L〕均较正常对照组〔(0 .5 3± 0 .0 9) g和 (374 .2 0± 92 .84 ) U/ L〕增高 ;经氨甲喋呤治疗后 2 4小时 ,胰腺湿重和淀粉酶均明显下降〔(0 .88± 0 .13) g和 (76 6 .33± 373.37) U / L ,P均 <0 .0 5〕。结论
Objective:To observe the effect of methotrexate (MTX) on modulation of the imbalance of proinflammatory and antiinflammatory cytokines in acute pancreatitis,and to investigate the mechanism of underlying treatment with MTX for acute pancreatitis.Methods:SD male rats were divided into 3 groups: ①normal animals served as control( n =6);②acute pancreatitis was induced by ductal injection of 5% sodium taurocholate in a dose of 1 0 ml/kg ( n =8);③after the pancreatitis was induced,animals were intravenously injected with MTX in a dose of 1 2 mg/kg.The animals were killed at 2,6 and 24 hours after operation,and blood samples were collected for measurement of tumor necrosis factorα(TNFα),interleukin(IL1),IL6 and IL10,and transforming growth factorβ(TGFβ)levels.The weight of pancreatic tissue,white blood cell count,and amylase were also determined.Results:Both proinflammatory cytokines(TNFα, IL1 , IL6 ) and the antiinflammatory cytokines (IL10,TGFβ) in blood were significantly increased after acute pancreatitis (all P <0 05).Treatment with MTX could markedly reduce serum TNFα, IL1 ,and IL6 levels at 2,6 and 24 hours postinjury (all P <0 05),together with decrease in IL10 as well as TGFβ level 24 hours later (all P <0 05).In addition,the severity of acute pancreatitis including amylase levels and the weight of pancreatic tissue,was also alleviated in animals treated with MTX.Conclusions:MTX as an immunosuppressive agent can inhibit both proinflammatory cytokines and antiinflammatory cytokines in acute pancreatitis, thereby regulating abnormal host immunity and alleviating the pathophysiological disorders of acute pancreatitis.
出处
《中国危重病急救医学》
CAS
CSCD
2002年第6期332-335,共4页
Chinese Critical Care Medicine
基金
国家教委部分高等医学院校博士点学科专项科研基金资助项目 (No.960 63 0 0 3 )