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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
【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。
【Abstract】 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.
【Key words】 Nuclear factor-kappaB; Antisense oligonucleotides; Acute necrotizing pancreatitis; Liposome; Proinflammatory cytokine;
- 【文献出处】 中华急诊医学杂志 ,Journal of Emergency Medicine , 编辑部邮箱 ,2005年05期
- 【分类号】R576
- 【被引频次】3
- 【下载频次】100