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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 investigate the effect of liposome-mediated p65 antisense oligonucleotide (ASODN) on acute hemorrhagic necrotizing pancreatitis (ANP) in rats. Methods 72 rats were randomly divided into sham operation group, pancreatitis group, liposome group, ASODN group (20OD ml), ASODN + liposome group and random ODN group. The pathological changes of pancreas were observed at 6h and 12h after operation. Serum amylase, serum IL-1, TNF-α, pancreatic tissue nuclear factor (NF-κB) activity changes. Results Compared with the sham operation group, the serum amylase activity, IL-1, TNF-α levels and the activity of NFκB in pancreatic tissue were significantly increased in all treatment groups (P <0.01). However, the differences in serum amylase activity No significant. Compared with the pancreatitis group, there were significant differences in pancreatic pathological score, serum IL-1, TNF-αand pancreatic NFκB activity between the liposome group and the random ODN group (P <0.05) Serum IL-1, TNF-α and NFκB activity in pancreas decreased in the plastid group (P <0.05), and the ASODN + liposome group decreased more obviously. Conclusion Liposome-mediated antisense oligonucleotide p65 can significantly inhibit the expression of serum proinflammatory cytokines in ANP rats and improve the pancreatic pathology, suggesting that NF-κB plays an important role in the pathogenesis of acute pancreatitis (AP) The key regulatory role, its p65 ASODN can be applied to the treatment of AP.