CAJ | 학술논문

目的研究蛋白酶体抑制剂MG-132对雨蛙肽诱导的急性胰腺炎(AP)小鼠核因子κB(NF-κB)与细胞间黏附分子1(ICAM-1)表达的影响.方法 45只BalB/c小鼠按随机数字表法分为9组,即对照3、6、12 h组,AP3、6、12 h组和MG-132 3、6、12 h组,每组5只.AP组小鼠雨蛙肽100μg/kg腹腔内注射诱导,1次/h,共6次.对照组则腹腔内注射相同剂最的生理盐水.MG-132组在AP诱导前30 min腹腔注射MG-132 10 mg/ks.检测血清淀粉酶和可溶性ICAM-1(sICAM-1)的浓度变化,观察胰腺的病理学变化,经免疫组化法检测胰腺组织中NF-κB的表达,采用半定量逆转录聚合酶链反应(RT-PCR)检测胰腺组织中ICAM-1 mRNA的表达.结果 MG-132各组血清淀粉酶(U/L)、血清sICAM-1(pg/ml)的浓度均低于相应时间点AP各组(1629±59、1794±123、2910±152比1282±61、1525±103、1809±117,133±10、157±10、217±43比106±6、135±4、163±19,P<0.05或P<0.01),MG-132各组胰腺组织的病理评分均分别低于相应时间点AP各组(5.7±1.0、7.1±1.2、9.6±2.1比3.2±1.0、5.3±1.0、6.9±0.8,P<0.05或P<0.01),MG-132组胰腺组织中NF-κB蛋白表达及ICAM-1 mRNA的表达均明显低于相应时间点AP各组(3.8±1.1、4.6±1.2、6.7±0.4比1.9±0.6、3.1±1.0、4.7±1.0,0.3±0.1、1.0±0.2、1.2±1.0比0.3±0.2、1.8±0.2、2.1±0.2,P<0.05或P<0.01)的表达.结论蛋白酶体抑制剂MG-132对雨蛙肽诱导的AP具有保护作用,其机制可能与抑制NF-κB的活化、下调包括黏附分子在内的细胞因子的表达有关.
목적 연구단백매체억제제MG-132대우와태유도적급성이선염(AP)소서핵인자κB(NF-κB)여세포간점부분자1(ICAM-1)표체적영향.방법 45지BalB/c소서안수궤수자표법분위9조,즉대조3、6、12 h조,AP3、6、12 h조화MG-132 3、6、12 h조,매조5지.AP조소서우와태100μg/kg복강내주사유도,1차/h,공6차.대조조칙복강내주사상동제최적생리염수.MG-132조재AP유도전30 min복강주사MG-132 10 mg/ks.검측혈청정분매화가용성ICAM-1(sICAM-1)적농도변화,관찰이선적병이학변화,경면역조화법검측이선조직중NF-κB적표체,채용반정량역전록취합매련반응(RT-PCR)검측이선조직중ICAM-1 mRNA적표체.결과 MG-132각조혈청정분매(U/L)、혈청sICAM-1(pg/ml)적농도균저우상응시간점AP각조(1629±59、1794±123、2910±152비1282±61、1525±103、1809±117,133±10、157±10、217±43비106±6、135±4、163±19,P<0.05혹P<0.01),MG-132각조이선조직적병리평분균분별저우상응시간점AP각조(5.7±1.0、7.1±1.2、9.6±2.1비3.2±1.0、5.3±1.0、6.9±0.8,P<0.05혹P<0.01),MG-132조이선조직중NF-κB단백표체급ICAM-1 mRNA적표체균명현저우상응시간점AP각조(3.8±1.1、4.6±1.2、6.7±0.4비1.9±0.6、3.1±1.0、4.7±1.0,0.3±0.1、1.0±0.2、1.2±1.0비0.3±0.2、1.8±0.2、2.1±0.2,P<0.05혹P<0.01)적표체.결론 단백매체억제제MG-132대우와태유도적AP구유보호작용,기궤제가능여억제NF-κB적활화、하조포괄점부분자재내적세포인자적표체유관.
Objective To investigate the effects of the proteasome inhibitor MG-132 upnon NF-κB and the expression of intercellular adhesion molecule-1 (ICAM-1) in cerulein-induced acute pancreatitis (AP) in mice. Methods Forty-five BalB/c mice were randomly allocated into nine groups: control 3, 6, 12 h group (n = 5) ; AP 3, 6, 12 h group (n = 5) and MG-132 3, 6, 12 h group (n = 5). AP group was induced by an ip injection of 100 μg/kg cerulein six times with a 1 h interval. Control group received physiological saline likewise. MG-132 group was injected ip with 10 mg/kg MG-132 at 30 min before induction of AP. The levels of serum amylase and soluble ICAM-1 (sICAM-1) were tested. The pathological changes of pancreas were observed. The expression of NF-κB proteins was examined by immunohistochemistry and the expression of ICAM-1 mRNA analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Results In MG-132 group, the levels of serum amylase (U/L) and sICAM-1 (pg/ml) markedly decreased in comparison with AP group (1629 ± 59, 1794 ± 123, 2910 ± 152 vs 1282 ±61, 1525±103, 1809±117, 133±10, 157±10, 217±43 vs 106±6, 135±4, 163±19, P<0.05 or P <0. 01) ; the scores of pathological changes decreased in pancreas (5.7 ± 1.0, 7. 1 ± 1.2, 9. 6 ± 2. 1 vs 3.2 ± 1.0, 5. 3 ± 1.0, 6. 9 ± 0. 8, P < 0. 05 or P < 0. 01) ; the expression of NF-κB protein (3.8 ± 1.1, 4.6±1.2, 6.7±0.4 vs 1.9±0.6, 3. 1 ± 1.0, 4.7 ± 1.0, P <0.05 or P <0.01) were significantly lowered than those in AP group. ICAM-1 mRNA also decreased more than those in AP group (0. 3±0. 1, 1.0±0.2,1.2±1.0 vs 0.3±0.2,1.8±0.2,2.1±0.2, P<0.05 or P<0.01). Conclusions The pmteasome inhibitor MG-132 can obviously improve the outcome of acute pancreatis. And the mechanism may be related to the down-regulated expression of cytokines, including adhesion molecules, through the suppression of NF-κB activation.