脂质体介导的p65反义寡核苷酸对大鼠急性出血坏死性胰腺炎的作用  

Effects of p65 antisense oligonucleotides liposome-mediated on acute necrotizing pancreatitis

作　　者：陈垦[1] 王念林[2] 龙友明[1] 兰雷[2] 王晖[3] 林振和[2] 刘学进[2] 

机构地区：[1]广东药学院临床医学系,广东省广州510224 [2]广东医学院附属医院消化内科 [3]广东医学院药理教研室

出　　处：《中华急诊医学杂志》2005年第5期398-401,共4页Chinese Journal of Emergency Medicine

基　　金：2002年广东高校自然科学研究项目(Z02044)

摘　　要：目的探讨脂质体介导的p65反义寡核苷酸(ASODN)对大鼠急性出血坏死性胰腺炎(ANP)的作用。方法72只大鼠随机分成假手术组、胰腺炎组、脂质体组、ASODN组(20OD ml)、ASODN+脂质体组、随机ODN组,观察各组大鼠术后6h及12h胰腺病理、血清淀粉酶、血清IL-1、TNF-α、胰腺组织核转录因子(NF-κB)活性的变化。结果同假手术组相比,各处理组的血清淀粉酶活性、IL-1、TNF-α水平、胰腺组织NFκB活性明显升高(P<0.01),但各处理组间的血清淀粉酶活性差异无显著性。同胰腺炎组相比,脂质体组和随机ODN组的胰腺病理评分、血清IL-1、TNF-α、胰腺组织NFκB活性的差异有显著性(P<0.05),而ASODN组和ASODN+脂质体组的胰腺病理评分、血清IL-1、TNF-α、胰腺组织NFκB活性下降(P<0.05),其中ASODN+脂质体组下降更为明显。结论脂质体介导的p65反义寡核苷酸可明显抑制ANP大鼠的血清致炎性细胞因子的表达,改善胰腺病理,提示NF-κB在急性胰腺炎(AP)的发病机制中起关键性调控作用,其p65ASODN可应用于AP的治疗。Objective To explore the effects of p65 antisense oligonucleotides liposome-mediated on rats with acute necrotizing pancreatitis.Method Seventy-two rats were divided into six groups:pseudo operation group,pancreatitis group,liposome group,antisense oligonucleotides group(20 OD/ml),antisense oligonucleotides+liposome group,and random oligonucleotides group.Pancreas histopathology,NF-kappa B activity,serum amylase activity,IL-1 level,and TNF-α in serum were detected at 6 hours and 12 hours after operation.Result Compared with pseudo operation group,the scores of pancreas histopathology,IL-1 level,TNF-α in serum,and pancreas NF-kappa B activity elevated markedly in all treatment groups at these two time points(P<0.05).But for serum amylase,no significant difference was detected among the treatment groups(P>0.05).Compared with pancreatitis group,there was significant difference in antisense oligonucleotides group or antisense oligonucleotides+liposome group,especially the latter group(P<0.05),but not in other treatment groups(P>0.05).Conclusion p65 antisense oligonucleotides liposome-mediated could significantly inhibit expression of proinflammatory cytokines on ANP rats and attenuate the inflammation development.It suggests that NF-kappa B play an important action in AP pathogenesis,and p65 antisense oligonucleotides might have therapeutice effects on acute pancreatitis.

关 键 词：急性出血坏死性胰腺炎 反义寡核苷酸 脂质体介导 p65 大鼠 NF-κB活性 急性胰腺炎(AP) TNF-α ASODN 血清淀粉酶活性 致炎性细胞因子 IL-1 胰腺组织 胰腺病理 病理评分 核转录因子 调控作用 发病机制 显著性 随机 性差异 

分 类 号：R576[医药卫生—消化系统]