α-黑素细胞刺激素对大鼠急性胰腺炎肺损伤的保护作用
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摘要
目的：探讨α-黑素细胞刺激素对大鼠急性胰腺炎及其所导致的肺损伤的作用。方法：1动物分组30只SD大鼠随机分为假手术组，SAP组，α-MSH处理组。2模型制备及检测指标SAP模型采用5％牛黄胆酸钠1ml／kg胰胆管内逆行注射建立。α-MSH预处理组于注射牛黄胆酸钠后1h在腹腔注射α-MSH0.25mg／kg。假手术组于胰胆管内逆行注射生理盐水。用链霉素抗生物素过氧化物酶连结法(streptavidin peroxidase conjugated method，SP)检测肺组织巨噬细胞移动抑制因子(MIF)表达，同时观察肺、胰腺的病理、湿／干重比，血清淀粉酶，腹水量。
结果：1．α-MSH对胰腺和肺湿／干比重的影响：湿／干重比的比较显示应用α-MSH后胰腺和肺湿／干重下降。差异有统计学意义(P＜0.05)。
2．α-MSH对肺组织和胰腺组织病理的影响：假手术组大鼠肺组织和胰腺组织光镜下未见明显病变，SAP组有明显肺和胰腺组织学损伤改变，α-MSH处理组对胰腺和肺组织学损伤程度的影响较SAP组有明显下降，差异有统计学意义(P＜0.05)。
3．α-MSH对肺组织MIF表达的影响：表中显示假手术组大鼠肺组织内很少有MIF表达阳性的细胞。α-MSH处理组与SAP组比较，MIF表达阳性强度较SAP组减少。差异有统计学意义(P＜0.05)。肺组织病理变化与MIF的表达成正相关。相关系数为r=0.579。
结论：α-MSH对急性胰腺炎本身和其所致的肺损伤有一定的治疗作用，其作用机制可能是通过抑制MIF的表达来抑制细胞因子的释放而减轻SAP所致的胰腺和肺损伤
Objective: To investigate the role ofα-MSH in acute lung injury (ALI) associated with severe acute pancreatitis (SAP).
Material and Method: A total of thirty Sprague-Dawley rats were randomly divided into sham operation group, SAP group andα-MSH treatment group. The model of SAP was established by retrograde pancreatic injection of sodium taurocholate(1 ml/kg). The model of sham operation group was established by retrograde pancreatic injection of 0.9% sodium chloride. The model ofα-MSH treatment group was the same as SAP group an hour later by celiac injection ofα-MSH. Intrapulmonary expression of MIF was assayed by streptavidin peroxidase conjugated method(SP). Meanwhile, serum level of amylase, ascites volume, pulmonary and pancreatic wet/dry weight ratio and pulmonary and pancreatic histological grading were also measured.
Results: 1.serum level of amlyse、pancreatic and pulmonary wet/dry weight ratio、the histological scores of pulmonary and pancrease、the expression of MIF in pulmonary in SAP groupwas very high. While in the sham operation group they were normal.
2.After the treatment ofα-MSH ,serum level of amlyse、pancreatic and pulmonary wet/dry weight ratio were markly decreased;the histological scores of pulmonary and pancrease and the expression of MIF in pulmonary were decreased,with statistical significance compared with the SAP group(P<0.01).
3.the expression of MIF in pulmonary had positive correlation with the score of lunginjury.r=0.579
Conclusion: The treatment ofα-MSH showed lung and pancreas protective eftect.Themechanism may be by the inhibitory action ofα-MSH on the expression of MIF thatcan inhibite the release of cytokine. Meanwhile ,it can reduce severity of SAP.
结果：1．α-MSH对胰腺和肺湿／干比重的影响：湿／干重比的比较显示应用α-MSH后胰腺和肺湿／干重下降。差异有统计学意义(P＜0.05)。
2．α-MSH对肺组织和胰腺组织病理的影响：假手术组大鼠肺组织和胰腺组织光镜下未见明显病变，SAP组有明显肺和胰腺组织学损伤改变，α-MSH处理组对胰腺和肺组织学损伤程度的影响较SAP组有明显下降，差异有统计学意义(P＜0.05)。
3．α-MSH对肺组织MIF表达的影响：表中显示假手术组大鼠肺组织内很少有MIF表达阳性的细胞。α-MSH处理组与SAP组比较，MIF表达阳性强度较SAP组减少。差异有统计学意义(P＜0.05)。肺组织病理变化与MIF的表达成正相关。相关系数为r=0.579。
结论：α-MSH对急性胰腺炎本身和其所致的肺损伤有一定的治疗作用，其作用机制可能是通过抑制MIF的表达来抑制细胞因子的释放而减轻SAP所致的胰腺和肺损伤
Objective: To investigate the role ofα-MSH in acute lung injury (ALI) associated with severe acute pancreatitis (SAP).
Material and Method: A total of thirty Sprague-Dawley rats were randomly divided into sham operation group, SAP group andα-MSH treatment group. The model of SAP was established by retrograde pancreatic injection of sodium taurocholate(1 ml/kg). The model of sham operation group was established by retrograde pancreatic injection of 0.9% sodium chloride. The model ofα-MSH treatment group was the same as SAP group an hour later by celiac injection ofα-MSH. Intrapulmonary expression of MIF was assayed by streptavidin peroxidase conjugated method(SP). Meanwhile, serum level of amylase, ascites volume, pulmonary and pancreatic wet/dry weight ratio and pulmonary and pancreatic histological grading were also measured.
Results: 1.serum level of amlyse、pancreatic and pulmonary wet/dry weight ratio、the histological scores of pulmonary and pancrease、the expression of MIF in pulmonary in SAP groupwas very high. While in the sham operation group they were normal.
2.After the treatment ofα-MSH ,serum level of amlyse、pancreatic and pulmonary wet/dry weight ratio were markly decreased;the histological scores of pulmonary and pancrease and the expression of MIF in pulmonary were decreased,with statistical significance compared with the SAP group(P<0.01).
3.the expression of MIF in pulmonary had positive correlation with the score of lunginjury.r=0.579
Conclusion: The treatment ofα-MSH showed lung and pancreas protective eftect.Themechanism may be by the inhibitory action ofα-MSH on the expression of MIF thatcan inhibite the release of cytokine. Meanwhile ,it can reduce severity of SAP.
引文
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[2] Renner IG, Savage WT 3rd, Pantoja JL, et al. Death due to acute pancreatitis. A retrospective analysis of 405 autopsy cases. Dig Dis Sci, 1985,30:1005-1018.
[3] 张圣道，韩天权，汤耀卿。重症急性胰腺炎临床新技术。人民军医出版社：131．
[4] Imrie CW, Ferguson JC, Murpgy D. Arterial hyoxia in acute pancreatitis .BR J Surg. 1997,64(3):185-188.
[5] Willemer S, Fedderse CO, Karges W, et al. lung injury in acute experimental pancreatitis in rats. I. Morphological studies. Int J Pancreatol, 1991,8(4):305-321.
[6] Lee WL, Downey GP. Neutrophil activation and acute lung injury. Curr Opin Crit Care. 2001,7(1):1-7.
[7] 中华医学会呼吸病学分会。急性肺损伤／急性呼吸窘迫综合征的诊断标准。中华结核和呼吸杂志。2000，23(24)：203．
[8] Calandra T, Berhagen J, Mitchell RA, et al. The macrophage is a important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med. 1994,179:1895-1902.
[9] Maxime V, Fitting C, Annane D. Corticoids normalize leukocyte production of macropgage migration inhivitory factor in septic shock. Infect Dis, 2005,191(1):138-144.
[10] 汤耀斌，徐公元，梁志忠等。巨噬细胞移动抑制因子在新生儿呼吸窘迫综合征发病中的作用。中华儿科杂志。2003，41(5)：363-364．
[11] Donnelly SC, Haslett C, Reid RT, et al. Regulatory role for maceration factor in acute respiratory distress syndrome. Nat Med, 1997,3:320-323.
[12] 郭禹标，谢灿茂。巨噬细胞移动抑制因子在急性呼吸窘迫综合征发病中的作用。中华结核和呼吸杂志。2002，25：337-340．
[13] Yoshitaka Sakai,Atsushi Masamune, Akihiko Satoh, et al. Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis. Gastroenterology, 2003,124:725-736.
[14] Catania A ,LiptonJM. Peptide modulation of fever and inflammation within the brain. Ann N YAcad Sci ,1998 ,856:62-68.
[15] 吴秀菊，田野平，周正芳等。α-M SH抑制内毒素血症大鼠不同组织表达巨噬细胞移动抑制因子。免疫学杂志。2001，17(4)：254-256．
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