CAJ | 학술논문

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(20 OD/mL)、ASODN＋脂质体组、随机ODN组,观察各组大鼠术后6 h及12 h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p65 ASODN对AP可能具有治疗效应.
목적 관찰지질체개도적p65반의과핵감산(ASODN)예처리대대서급성출혈배사성이선염(ANP)적항염작용.방법 통과이담관적주사법유도대서출혈배사성이선염.기중72지대서분성가수술조,이선염조、지질체조、ASODN조(20 OD/mL)、ASODN＋지질체조、수궤ODN조,관찰각조대서술후6 h급12 h이선병리、혈청정분매、이선조직수과양화물매(MPO)、병이철(MDA)급NF-κB활성적변화.결과 동가수술조상비,각처리조적혈청정분매활성、MDA、MPO수평、이선조직NF-κB활성명현승고(P＜0.01).각처리조간적혈청정분매적차별무통계학의의.동이선염조상비,지질체조화수궤ODN조적이선병리평분、MDA、MPO、이선조직NF-κB활성적차별무통계학의의(P＞0.05),이ASODN조、ASODN＋지질체조적이선병리평분,MPO、MDA、이선조직NF-κB활성하강(P＜0.05),기중ASODN＋지질체조하강경위명현.결론 지질체개도적p65반의과핵감산능감경ANP대서적염증발전,NF-κB삼여료AP적발병궤제,기p65 ASODN대AP가능구유치료효응.
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.