阿拓莫兰对重症急性胰腺炎大鼠肺损伤的保护作用
摘要
目的:研究阿拓莫兰是否对重症急性胰腺炎大鼠肺损伤有保护作用;探讨重症急性胰腺炎肺损伤的发病机制。
方法:54只SD大鼠随机分为对照组(n=18),模型组(SAP组,n=18)和治疗组(阿拓莫兰治疗组,n=18)。采用十二指肠乳头逆行插管胰胆管注射5%的牛磺胆酸钠的方法复制大鼠SAP模型,各组大鼠分别于建模后3h、6h、12h剖杀,检测血清淀粉酶,测定肺含水量,肺组织病理切片HE染色后观察形态学变化,RT-PCR法检测肺组织中TNF-α、LIF基因的表达水平。
结果:治疗组各时间点血清淀粉酶均低于模型组(P<0.05),但仍高于对照组(P<0.05);治疗组较模型组肺含水量减少(P<0.05),较对照组明显为高(P<0.05);肺组织病理示对照组无明显形态学变化,肺损伤程度治疗组明显轻于模型组;对照组肺组织中未见明显的LIF基因表达,建摸后3h、6h、12h治疗组TNF-α、LIF基因的表达水平均低于模型组(P<0.05),模型组及治疗组大鼠肺组织中TNF-α基因的表达水平均高于对照组(P<0.05)。
结论:阿拓莫兰能够降低重症急性胰腺炎大鼠外周血淀粉酶水平、降低肺组织中TNF-α、LIF基因的表达水平、降低肺部炎症程度;阿拓莫兰对重症急性胰腺炎大鼠肺损伤具有保护作用。
Objective:To investigate whether Atomolan has the protective effect on lung injury in rats with severe acute pancreatitis(SAP) and investigate the mechanism of severe acute pancreatitis associated lung injury.
Methods:Fifty-four Spragwe Dawley rats were randomly divided into three groups:normal control(n=18)group,model(SAP,n=18)group and herbal(n=18) group.Model group and herbal group were induced by retrograde injection of 5% sodium taurocholate into the pancreatobiliary duct.Herbal group were injected intravenously at 3h,6h,12h after induced SAP models.The serum level of amylase were examined at 3h,6h,12h.Lung water content were measured and the lobe of rat lung were dissected for histology.The expression of pulmonary TNF-αmRNA and LIF mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).
Results:The serum level of amylase were released significantly in herbal group in comparison with that in model group(P<0.05) and the lung water content level in herbal group was released compared with model group(P<0.05);Similarly,the level of pulmonary TNF-αmRNA and LIF mRNA expressions were both released significantly in herbal group compared with model group(P<0.05).LIF mRNA was not examined in normal control group.
Conclusion:After treated with Atomolan,the serum level of amylase and the level of pulmonary TNF-αmRNA and LIF mRNA of lung tissue released significantly associated with SAP;Treatment with Atomolan could prevent lung injury of rats with SAP.
方法:54只SD大鼠随机分为对照组(n=18),模型组(SAP组,n=18)和治疗组(阿拓莫兰治疗组,n=18)。采用十二指肠乳头逆行插管胰胆管注射5%的牛磺胆酸钠的方法复制大鼠SAP模型,各组大鼠分别于建模后3h、6h、12h剖杀,检测血清淀粉酶,测定肺含水量,肺组织病理切片HE染色后观察形态学变化,RT-PCR法检测肺组织中TNF-α、LIF基因的表达水平。
结果:治疗组各时间点血清淀粉酶均低于模型组(P<0.05),但仍高于对照组(P<0.05);治疗组较模型组肺含水量减少(P<0.05),较对照组明显为高(P<0.05);肺组织病理示对照组无明显形态学变化,肺损伤程度治疗组明显轻于模型组;对照组肺组织中未见明显的LIF基因表达,建摸后3h、6h、12h治疗组TNF-α、LIF基因的表达水平均低于模型组(P<0.05),模型组及治疗组大鼠肺组织中TNF-α基因的表达水平均高于对照组(P<0.05)。
结论:阿拓莫兰能够降低重症急性胰腺炎大鼠外周血淀粉酶水平、降低肺组织中TNF-α、LIF基因的表达水平、降低肺部炎症程度;阿拓莫兰对重症急性胰腺炎大鼠肺损伤具有保护作用。
Objective:To investigate whether Atomolan has the protective effect on lung injury in rats with severe acute pancreatitis(SAP) and investigate the mechanism of severe acute pancreatitis associated lung injury.
Methods:Fifty-four Spragwe Dawley rats were randomly divided into three groups:normal control(n=18)group,model(SAP,n=18)group and herbal(n=18) group.Model group and herbal group were induced by retrograde injection of 5% sodium taurocholate into the pancreatobiliary duct.Herbal group were injected intravenously at 3h,6h,12h after induced SAP models.The serum level of amylase were examined at 3h,6h,12h.Lung water content were measured and the lobe of rat lung were dissected for histology.The expression of pulmonary TNF-αmRNA and LIF mRNA were detected by semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).
Results:The serum level of amylase were released significantly in herbal group in comparison with that in model group(P<0.05) and the lung water content level in herbal group was released compared with model group(P<0.05);Similarly,the level of pulmonary TNF-αmRNA and LIF mRNA expressions were both released significantly in herbal group compared with model group(P<0.05).LIF mRNA was not examined in normal control group.
Conclusion:After treated with Atomolan,the serum level of amylase and the level of pulmonary TNF-αmRNA and LIF mRNA of lung tissue released significantly associated with SAP;Treatment with Atomolan could prevent lung injury of rats with SAP.
引文
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[1] 杨雪菲,王春友.对重型急性胰腺炎的认识现况[J].中国综合临床,2005,21(1):95.
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[2] Lankish RG,Droge M,Becher R.Pulmonary infiltrative signs of severe acute pancreatitis.Int J pancreatology,1996,19(2):113-115.
[3] Scott P.Vitamin C status in patients with acute pancreatitis. Br J Surg,1993,80(6):750-754.
[4] Steer ML.Pancreatitis Severity:Who calls the Shots? Gastroenterology, 2002,122(4):1168- 1170.
[5] Tsukahara Y,Morisaki T,Horita Y,et al.Phospholipase A2 mediates nitric oxide production by alveolar macrophages and acute lung injury in pancreatitis.Ann Surg,1999,229 (3):385-392.
[6] 程石,何三光,张佳林.肺泡巨噬细胞活化在急性坏死性胰腺炎大鼠肺损伤中的作用.中华外科杂志,2002,40(8):609-612.
[7] Madhav BT,Shabbir MH.Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. Journal of Pathology,2004,202:145-156.
[8] Grewal HP,Moheyel DA,Gaber L,et al.Ameliotation of thephysiological and biochemical changes of acute pancreatitis using an anti-TNF-α polyclonal antibody.Am J Surg, 1994,167(1):214.
[9] 肖雪明,邹声泉.肿瘤坏死因子与急性胰腺炎.国外医学外科学分册,1997,24(6):331.
[10] 吕孝东,刘银寿,吴清荣.大鼠急性胰腺炎外周血 TNF-α水平变化研究.苏州医学院学报,1999,19(1):7.
[11] Szepietowski J,Reich A.Leukaemia inhibitory factor(LIF) : structure and biological activity.Postepy Hig Med Dosw(Online)2004,58:243-251.
[12] Chabaud M,Fossiez F,Taupin JL,et al.Enhancing effect of IL-17 on IL-1 induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by the cytokines.J Immunol,1998,161:409-414.
[13] Grosset C,Taupin JL,Lemercier C,et al. Leukaemia inhibitory factor expression is inhibited by glucocorticoids through post-transcriptional mechanisms.Cytokine,1999,11:29-36.
[14] Kerr BJ,Patterson PH.Potent pro-inflammatory actions of leukemia inhibitory factor in the spinal cord of the adult mouse.Exp Neurol,2004,188:391-407.
[15] Lankisch PG,Rahlf G,Koop H.Pulmonary complications in fatal acute hemorrhagic pancreatitis.Dig Dis Sci,1983,28:110-116.
[16] Zheng X,Knight DA,Zhou D,et al.Leukemia inhibitory factor is synthesized and released by human eosinophils and modulates activation state and chemotaxis.J Allergy Clin Immunol 1999,104:136-144.
[17] Sun W,Watanabe Y,Wang ZQ.Expression and significance of ICAM-1 and its counter receptors LFA-1 and Mac-1 in experimental acute pancreatitis of rats. World J Gastroenterol, 2006,12(31):5005-5009.
[18] Bhatia M,Brady M.Treatment with neutralizing antibody against cytokine induced neutrophil chemoattractant(CINC) protects rats against acute pancreatitis associated lung injury.GUT, 2000,47:838-844.
[19] Li ZD,Ma QY,Wang CA.Effect of resveratrol on pancreatic oxygen free radicals in rats with severe acute pancreatitis.World J Gastroenterol,2006,12(1):137-140.
[20] Leff JA.Increased serum catalase activity in septic patients with the adult respiratory distress syndrome Am revrespirdis,1992,146(4):985-989.
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