雨蛙素及脂多糖诱导小鼠急性胰腺炎效果分析
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摘要
目的观察雨蛙素(CAE)诱导小鼠急性胰腺炎模型中胰腺及肺组织损伤时间变化规律;对比雨蛙素及脂多糖(LPS)不同给药方案诱导的小鼠急性胰腺炎模型效果。方法雨蛙素不同给药频次以及雨蛙素联合脂多糖诱导小鼠急性胰腺炎模型,收集小鼠血浆以淀粉-碘比色法检测淀粉酶活性;取胰腺及肺组织行HE染色观察组织损伤严重程度。结果 CAE7组小鼠胰腺及肺组织损伤在4 h达高峰,24 h开始修复,5 d基本恢复正常;造模后4 h,CAE7组和CAE9组小鼠血淀粉酶活性较对照组升高[(6 461±1 078)U/dl比(3 093±331)U/dl;(6 821±495)U/dl比(3 093±331)U/dl,P<0.001],且CAE7+LPS组较CAE9组更高[(8 912±465)U/dl比(6 821±495)U/dl,P<0.001],CAE7组和CAE9组小鼠胰腺组织病理评分较对照组升高(4.750±0.524比0±0;4.917±0.664比0±0,P<0.001),且CAE7+LPS组较CAE9组更高(7.167±0.258比4.917±0.664,P<0.001)。结论雨蛙素50μg/kg连续7次给药可诱导出小鼠急性胰腺炎模型,增加给药频次未见胰腺组织损伤加重,而联用脂多糖可加重急性胰腺炎模型严重程度。
Objective To observe the time dependent changes of pancreas and lung injury in mice acute pancreatitis induced by caerulein,and compare the effects of mice acute pancreatitis model induced by different injection protocols of caerulein and lipopolysaccharides. Methods Acute pancreatitis were induced by different injection frequency of caerulein or caerulein combined with lipopolysaccharides,and plasma amylase activity was detected by starch-iodine colorimetry,and pancreas and lung injury severity was observed on paraffin section after HE staining. Results The injury of pancreas and lung in mice acute pancreatitis induced by caerulein was most severe at4 h,which began to repair at 24 h,and basically returned to normal at 5 d. 4 h after last injection,the amylase activity in CAE7 group and CAE9 group was higher than that in the control group( 6 461 ± 1 078 U/dl vs 3 093 ±331 U/dl; 6 821 ± 495 U/dl vs 3 093 ± 331 U/dl,all P < 0. 001),and CAE7 + LPS group was higher than in CAE9 group[( 8 912±465) U/dl vs( 6 821±495) U/dl,P<0. 001],the histological score in CAE7 group andCAE9 group was higher than that in the control group( 4. 750 ± 0. 524 vs 0 ± 0; 4. 917 ± 0. 664 vs 0 ± 0,all P <0. 001),and that in CAE7 + LPS group was higher than in CAE9 group( 7. 167 ± 0. 258 vs 4. 917 ± 0. 664,P <0. 001). Conclusions Mice acute pancreatitis can be successfully induced by 7 i. p. injections of caerulein( 50 μg/kg body weight) at 1-hour intervals,caerulein combined with lipopolysaccharides.
Objective To observe the time dependent changes of pancreas and lung injury in mice acute pancreatitis induced by caerulein,and compare the effects of mice acute pancreatitis model induced by different injection protocols of caerulein and lipopolysaccharides. Methods Acute pancreatitis were induced by different injection frequency of caerulein or caerulein combined with lipopolysaccharides,and plasma amylase activity was detected by starch-iodine colorimetry,and pancreas and lung injury severity was observed on paraffin section after HE staining. Results The injury of pancreas and lung in mice acute pancreatitis induced by caerulein was most severe at4 h,which began to repair at 24 h,and basically returned to normal at 5 d. 4 h after last injection,the amylase activity in CAE7 group and CAE9 group was higher than that in the control group( 6 461 ± 1 078 U/dl vs 3 093 ±331 U/dl; 6 821 ± 495 U/dl vs 3 093 ± 331 U/dl,all P < 0. 001),and CAE7 + LPS group was higher than in CAE9 group[( 8 912±465) U/dl vs( 6 821±495) U/dl,P<0. 001],the histological score in CAE7 group andCAE9 group was higher than that in the control group( 4. 750 ± 0. 524 vs 0 ± 0; 4. 917 ± 0. 664 vs 0 ± 0,all P <0. 001),and that in CAE7 + LPS group was higher than in CAE9 group( 7. 167 ± 0. 258 vs 4. 917 ± 0. 664,P <0. 001). Conclusions Mice acute pancreatitis can be successfully induced by 7 i. p. injections of caerulein( 50 μg/kg body weight) at 1-hour intervals,caerulein combined with lipopolysaccharides.
引文
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[9]张晓音,吴旻,李雨萌,等.脂多糖的效应及其机理研究进展[J].动物医学进展,2015,36:133-136.
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[12]Tang M,Zong P,Zhang T,et al.Lipoprotein lipase genedefcient mice with hypertriglyceridaemia associated with acute pancreatitis[J].Acta Cir Bras,2016,31:655-660.
[13]Chan LK,Gerstenlauer M,Konukiewitz B,et al.Epithelial NEMO/IKKγlimits fibrosis and promotes regeneration during pancreatitis[J].Gut Published Online First:27 July 2016.doi:11.1136/gutjnl-2015-311028.
[14]金畅,李继承.雨蛙素联合脂多糖致小鼠重症急性胰腺炎模型的建立及其机理的探讨[J].实验生物学报,2003,36:91-98.
[2]Lampel M,Kern HF.Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue[J].Virchows Arch A Pathol Anat Histol,1977,373:97-117.
[3]周英,马成才,吴运福,等.不同剂量雨蛙素诱导小鼠急性胰腺炎模型的对比研究[J].现代生物医学进展,2016,16:6804-6807.
[4]Pan Y,Li Y,Gao L,et al.Development of a novel model of hypertriglyceridemic acute pancreatitis in mice[J].Sci Rep,2017,7:1-10.
[5]Iyer S,Park MJ,Moons D,et al.Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis[J].Biochem Biophys Res Commun,2017,482:1346-1352.
[6]Dong Z,Shang H,Chen YQ,et al.Sulforaphane protects pancreatic acinar cell injury by modulating Nrf2-mediated oxidative stress and NLRP3 inflammatory pathway[J].Oxid Med Cell Longev,2016,7:1-12.
[7]Wang Y,Kayoumu A,Lu G,et al.Corrigendum:experimental models in syrian golden hamster replicate human acute pancreatitis[J].Sci Rep,2016,6:1-9.
[8]郑英强,黄娟,曾凡才,等.雨蛙素及脂多糖在小鼠急性胰腺炎建模中的应用[J].世界华人消化杂志,2014,22:4068-4074.
[9]张晓音,吴旻,李雨萌,等.脂多糖的效应及其机理研究进展[J].动物医学进展,2015,36:133-136.
[10]Yu QH,Guo JF,Chen Y,et al.Captopril pretreatment protects the lung against severe acute pancreatitis induced injury via inhibiting angiotensin II production and suppressing Rho/ROCK pathway[J].Kaohsiung J Med Sci,2016,32:439-445.
[11]陈杏田,杨元生,陈垦,等.急性胰腺炎实验动物模型的研究进展[J].中华全科医学,2017,15:857-860.
[12]Tang M,Zong P,Zhang T,et al.Lipoprotein lipase genedefcient mice with hypertriglyceridaemia associated with acute pancreatitis[J].Acta Cir Bras,2016,31:655-660.
[13]Chan LK,Gerstenlauer M,Konukiewitz B,et al.Epithelial NEMO/IKKγlimits fibrosis and promotes regeneration during pancreatitis[J].Gut Published Online First:27 July 2016.doi:11.1136/gutjnl-2015-311028.
[14]金畅,李继承.雨蛙素联合脂多糖致小鼠重症急性胰腺炎模型的建立及其机理的探讨[J].实验生物学报,2003,36:91-98.