【摘要】 目的观察脂质体介导的p65反义寡核苷酸(ASODN)预处理对大鼠急性出血坏死性胰腺炎(ANP)的抗炎作用。方法通过胰胆管的注射法诱导大鼠出血坏死性胰腺炎。其中72只大鼠分成假手术组,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、胰腺组织髓过氧化物酶(MPO)、丙二醛(MDA)及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、MDA、MPO水平、胰腺组织NF κB活性明显升高(P<0. 01)。各处理组间的血清淀粉酶的差别无统计学意义。同胰腺炎组相比,脂质体组和随机ODN组的胰腺病理评分、MDA、MPO、胰腺组织NF κB活性的差别无统计学意义(P>0. 05),而ASODN组、ASODN+脂质体组的胰腺病理评分,MPO、MDA、胰腺组织NF κB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反义寡核苷酸能减轻ANP大鼠的炎症发展,NF κB参与了AP的发病机制,其p65ASODN对AP可能具有治疗效应。更多还原

【Abstract】 Objective To study the effects of liposome-mediated p65 antisense oligonucleotide(ASODN) on acute necrotic pancreatitis(ANP) in rat. Methods Rat ANP was induced with the injection of 5% sodium taurocholate (STC, 1 mL/kg body weight) into rat’s biliopancreatic duct. 72 male Sprague-Dawley (S-D) rats were randomly divided into six groups: (1) pseudo-operation group (n=12); (2) ANP group (n=12); (3) lipofectin group(n=12); (4) ASODN group (n=12); (5) ASODN+liposome group (n=12); (6) random oligonucleotide group(n=12). Rats were bled to death 6 h (n=6) or 12 h (n=6) after operation respectively. NF-κB DNA-binding in pancreas was examined by electrophoretic mobility shift assays (EMSA). Pancreas inflammation and damage were assessed by macroscopical and histological criteria. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) level of pancreas and amylase activity in serum were also measured. Results Compared with pseudo-operation group, the scores of pancreas histopathology, level of MPO, MDA and NF-κB activity increased markedly in all treatment groups (P<0.05). But for serum amylase, no significant difference was detected among the treatment groups (P>0.05). Compared with ANP group, the scores of pancreas histopathology, levels of MDA, MPO and NF-κB activity showed significant decrease in ASODN group or ASODN+ liposome group (P<0.05), especially in the latter group, but there was no difference in other treatment groups (P>0.01). Conclusion Liposome-mediated p65 antisense oligonucleotides can significantly reduce the inflammatory process in rat with ANP. It suggests that NF- kappa B may play an important role in AP pathogenesis, and p65 antisense oligonucleotides may have therapeutic effects on acute pancreatitis.更多还原