PI3K/PKB信号转导通路在重症急性胰腺炎急性肺损伤中的作用机制研究
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摘要
第一部分重症急性胰腺炎急性肺损伤大鼠模型的制备
目的探讨BD针在重症急性胰腺炎急性肺损伤研究中大鼠模型建立的应用改良。方法健康成年雄性SD大鼠40只,随机分为假手术组(n=10)、模型组(n=30),应用BD静脉留置针经十二指肠乳头逆行胰胆管注入4%牛磺胆酸(0.1ml/kg),建立重症急性胰腺炎急性肺损伤大鼠模型。模型组在建模后3h,6h,12h检测大鼠血淀粉酶、血气分析、腹水量、肺含水量,光镜下进行胰腺和肺组织病变程度评分。假手术组在术后12h检测上述相关指标。结果模型组较假手术组血淀粉酶、腹水量、肺含水率、PaCO2、胰腺和肺组织学评分明显升高(P＜0.05)。同时PaO2,氧合指数明显降低(P＜0.05)。结论应用BD静脉留置针能有效制备简便,易复制,稳定性好的重症急性胰腺炎急性肺损伤大鼠模型。
第二部分ICAM-1在重症急性胰腺炎早期急性肺损伤发病中的作用研究
目的探讨细胞间粘附分子-1(ICAM-1)在大鼠重症急性胰腺炎早期急性肺损伤发病中的作用机制。方法健康成年雄SD大鼠40只,随机分为假手术组(S0组,n=10)、实验组(SAP组,n=30),BD针胰胆管逆行注入牛磺胆酸法,建立重症急性胰腺炎急性肺损伤大鼠模型。SAP组在建模后3h,6h,12h检测血淀粉酶、血气分析、肺含水率,肺组织髓过氧化物酶(Myeloperoxidase, MPO)活性,光镜下进行胰腺和肺组织病变程度评分。免疫组化法检测肺组织ICAM-1的表达,结果应用Image-Pro Plus 6.0图像分析系统定量分析。S0组在术后12h检测上述相关指标。结果制模后肺组织ICAM-1表达在3h后逐渐上升,持续升高达12h(P<0.05)。肺损伤程度逐渐加重,组织含水量及MPO活性逐渐升高(P<0.05),PaO2,氧合指数明显降低(P<0.05)。ICAM-1的表达量与肺MPO活性,肺组织病理学评分呈正相关(r=0.862,r=0.842,P<0.05)。结论ICAM-1参与了重症急性胰腺炎早期并发急性肺损伤发病的启动和进展过程。
第三部分PI3K/PKB信号转导通路在重症急性胰腺炎急性月伤中的活性变化
目的探讨重症急性胰腺炎急性肺损伤中磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/PKB)信号转导通路的活性变化规律。方法健康成年雄SD大鼠40只,随机分为S0组(n=10)、SAP各组(n=30),BD针胰胆管逆行注入牛磺胆酸法,建立重症急性胰腺炎急性肺损伤大鼠模型。免疫组化法检测肺组织ICAM-1和p-PKB的表达,蛋白印迹(Western Blot)法检测PI3K/PKB信号通路的活性变化。S0组在术后12h检测上述相关指标。结果制模后3h随p-PKB的活性逐步增强,ICAM-1表达逐渐增多,两者呈正相关(r=0.772, P<0.05);Western Blot检测结果提示PI3K/PKB信号转导通路逐步被激活,至12h达到峰值；期间肺损伤程度逐渐加重,组织含水量及MPO活性逐渐升高(P<0.05),PaO2明显降低(P<0.05)。PI3K/PKB信号转导通路活性与肺损伤程度呈正相关(r=0.844,P3K/PKB信号传导通路逐步被激活,其通过上调肺组织ICAM-1的表达和促进白细胞在肺组织中的浸润,促发急性肺损伤的发生和进展。
Part 1:The preparation of rat models of severe acute pancreatitis with acute lung injury
Objective To investigate the improvement of BD Intravenous Catheters used in inducing the model of acute lung injury with severe acute pancreatitis in rats. Methods Total 40 healthy adult male SD rats were randomly divided into 2 groups, SO group(n=10), SAP group(n=30), inject 4% taurocholate (0.1 ml/kg) retrograde biliopancreatic ducts by using BD Intravenous Catheters via duodenal papilla. The serum amylase, blood gas analysis, ascites volume, lung water content and the pathological score of pancreas and lung structure under light microscope were recorded when the SAP model were induced in 3 h,6 h and 12 h.The relative data mentioned as above also detected in SO group after 12h. Results The score of the SAP group is evidently higher than the SO group in blood amylase, ascites volume, lung water content, PaCO2, pancreas and lung histology (P<0.05). Meanwhile, PaO2, oxygenation index is decreased evidently (P<0.05). Conclusion It can efficiently establish simple, easily to reproduce and stability rat model of acute lung injury with severe acute pancreatitis by using BD intravenous Catheters.
Part 2:Study the effect of ICAM-1 on pathogenesis of acute lung injury in rats with severe acute pancreatitis.
Objective To investigate the mechanism of intercellular adhesion molecule-1 (ICAM-1) on pathogenesis of acute lung injury in rats with severe acute pancreatitis.
Methods 40 healthy adult male SD rats were randomly divided into 2 groups, SO group(n=10),SAP group(n=30),inject taurocholate retrograde biliopancreatic ducts by using BD Intravenous Catheters to establish the rat model of acute lung injury with severe acute pancreatitis. The serum amylase, blood gas analysis, lung water content, MPO activity in lung were detected and the score of the pancreas and lung lesion were recorded, when the SAP model were induced in 3h,6h and 12h. Detect the expression of ICAM-1 in lung tissue by immunohistochemistry, and do the quantitative analysis for it by using Image-Pro Plus 6.0 analysis system. The relative data mentioned as above also detected in SO group after 12h. Results The ICAM-1 expression in lung tissue gradually increased after 3h to 12h (P<0.05). The lung injury becomes more and more serious, water content and MPO activity also increased gradually (P <0.05).Meanwhile the PaO2, oxygenation index decreased evidently (P<0.05). It was positively correlated between ICAM-1 expression, lung lesion and lung MPO activity (r=0.862,r=0.842, P<0.05). Conclusion ICAM-1 involved in pancreatitis start and progress of the disease of severe acute pancreatitis complicated by acute lung injury in rats.
Part 3:The activity changes of PI3K/PKB signal transduction pathway in rats of acute lung injury with severe acute pancreatitis.
Objective To study the signal transduction pathway activity changes of PI3K/PKB in rats of acute lung injury with severe acute pancreatitis. Methods 40 healthy adult male SD rats were randomly divided into 2 groups, SO group (n=10), SAP group (n=30), inject taurocholate retrograde biliopancreatic ducts by using BD Intravenous Catheters to establish the rat model of acute lung injury with severe acute pancreatitis. When the SAP model were induced in 3h,6h and 12h, detect the expression of ICAM-1 and p-PKB. The expression of ICAM-1 and p-PKB in lung tissue by immunohistochemistry and the activity change of PI3K/PKB signal pathway by protein blot (Western Blot) assay were detected. The relative data mentioned as above also detected in SO group after 12h. Results 3h after molding with the p-PKB activity gradually increased, ICAM-1 expression increased, which were positively correlated (r=0.772, P<0.05); Western Blot test results shows that the PI3K/PKB signaling pathway is activated
目的探讨BD针在重症急性胰腺炎急性肺损伤研究中大鼠模型建立的应用改良。方法健康成年雄性SD大鼠40只,随机分为假手术组(n=10)、模型组(n=30),应用BD静脉留置针经十二指肠乳头逆行胰胆管注入4%牛磺胆酸(0.1ml/kg),建立重症急性胰腺炎急性肺损伤大鼠模型。模型组在建模后3h,6h,12h检测大鼠血淀粉酶、血气分析、腹水量、肺含水量,光镜下进行胰腺和肺组织病变程度评分。假手术组在术后12h检测上述相关指标。结果模型组较假手术组血淀粉酶、腹水量、肺含水率、PaCO2、胰腺和肺组织学评分明显升高(P＜0.05)。同时PaO2,氧合指数明显降低(P＜0.05)。结论应用BD静脉留置针能有效制备简便,易复制,稳定性好的重症急性胰腺炎急性肺损伤大鼠模型。
第二部分ICAM-1在重症急性胰腺炎早期急性肺损伤发病中的作用研究
目的探讨细胞间粘附分子-1(ICAM-1)在大鼠重症急性胰腺炎早期急性肺损伤发病中的作用机制。方法健康成年雄SD大鼠40只,随机分为假手术组(S0组,n=10)、实验组(SAP组,n=30),BD针胰胆管逆行注入牛磺胆酸法,建立重症急性胰腺炎急性肺损伤大鼠模型。SAP组在建模后3h,6h,12h检测血淀粉酶、血气分析、肺含水率,肺组织髓过氧化物酶(Myeloperoxidase, MPO)活性,光镜下进行胰腺和肺组织病变程度评分。免疫组化法检测肺组织ICAM-1的表达,结果应用Image-Pro Plus 6.0图像分析系统定量分析。S0组在术后12h检测上述相关指标。结果制模后肺组织ICAM-1表达在3h后逐渐上升,持续升高达12h(P<0.05)。肺损伤程度逐渐加重,组织含水量及MPO活性逐渐升高(P<0.05),PaO2,氧合指数明显降低(P<0.05)。ICAM-1的表达量与肺MPO活性,肺组织病理学评分呈正相关(r=0.862,r=0.842,P<0.05)。结论ICAM-1参与了重症急性胰腺炎早期并发急性肺损伤发病的启动和进展过程。
第三部分PI3K/PKB信号转导通路在重症急性胰腺炎急性月伤中的活性变化
目的探讨重症急性胰腺炎急性肺损伤中磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/PKB)信号转导通路的活性变化规律。方法健康成年雄SD大鼠40只,随机分为S0组(n=10)、SAP各组(n=30),BD针胰胆管逆行注入牛磺胆酸法,建立重症急性胰腺炎急性肺损伤大鼠模型。免疫组化法检测肺组织ICAM-1和p-PKB的表达,蛋白印迹(Western Blot)法检测PI3K/PKB信号通路的活性变化。S0组在术后12h检测上述相关指标。结果制模后3h随p-PKB的活性逐步增强,ICAM-1表达逐渐增多,两者呈正相关(r=0.772, P<0.05);Western Blot检测结果提示PI3K/PKB信号转导通路逐步被激活,至12h达到峰值；期间肺损伤程度逐渐加重,组织含水量及MPO活性逐渐升高(P<0.05),PaO2明显降低(P<0.05)。PI3K/PKB信号转导通路活性与肺损伤程度呈正相关(r=0.844,P
Part 1:The preparation of rat models of severe acute pancreatitis with acute lung injury
Objective To investigate the improvement of BD Intravenous Catheters used in inducing the model of acute lung injury with severe acute pancreatitis in rats. Methods Total 40 healthy adult male SD rats were randomly divided into 2 groups, SO group(n=10), SAP group(n=30), inject 4% taurocholate (0.1 ml/kg) retrograde biliopancreatic ducts by using BD Intravenous Catheters via duodenal papilla. The serum amylase, blood gas analysis, ascites volume, lung water content and the pathological score of pancreas and lung structure under light microscope were recorded when the SAP model were induced in 3 h,6 h and 12 h.The relative data mentioned as above also detected in SO group after 12h. Results The score of the SAP group is evidently higher than the SO group in blood amylase, ascites volume, lung water content, PaCO2, pancreas and lung histology (P<0.05). Meanwhile, PaO2, oxygenation index is decreased evidently (P<0.05). Conclusion It can efficiently establish simple, easily to reproduce and stability rat model of acute lung injury with severe acute pancreatitis by using BD intravenous Catheters.
Part 2:Study the effect of ICAM-1 on pathogenesis of acute lung injury in rats with severe acute pancreatitis.
Objective To investigate the mechanism of intercellular adhesion molecule-1 (ICAM-1) on pathogenesis of acute lung injury in rats with severe acute pancreatitis.
Methods 40 healthy adult male SD rats were randomly divided into 2 groups, SO group(n=10),SAP group(n=30),inject taurocholate retrograde biliopancreatic ducts by using BD Intravenous Catheters to establish the rat model of acute lung injury with severe acute pancreatitis. The serum amylase, blood gas analysis, lung water content, MPO activity in lung were detected and the score of the pancreas and lung lesion were recorded, when the SAP model were induced in 3h,6h and 12h. Detect the expression of ICAM-1 in lung tissue by immunohistochemistry, and do the quantitative analysis for it by using Image-Pro Plus 6.0 analysis system. The relative data mentioned as above also detected in SO group after 12h. Results The ICAM-1 expression in lung tissue gradually increased after 3h to 12h (P<0.05). The lung injury becomes more and more serious, water content and MPO activity also increased gradually (P <0.05).Meanwhile the PaO2, oxygenation index decreased evidently (P<0.05). It was positively correlated between ICAM-1 expression, lung lesion and lung MPO activity (r=0.862,r=0.842, P<0.05). Conclusion ICAM-1 involved in pancreatitis start and progress of the disease of severe acute pancreatitis complicated by acute lung injury in rats.
Part 3:The activity changes of PI3K/PKB signal transduction pathway in rats of acute lung injury with severe acute pancreatitis.
Objective To study the signal transduction pathway activity changes of PI3K/PKB in rats of acute lung injury with severe acute pancreatitis. Methods 40 healthy adult male SD rats were randomly divided into 2 groups, SO group (n=10), SAP group (n=30), inject taurocholate retrograde biliopancreatic ducts by using BD Intravenous Catheters to establish the rat model of acute lung injury with severe acute pancreatitis. When the SAP model were induced in 3h,6h and 12h, detect the expression of ICAM-1 and p-PKB. The expression of ICAM-1 and p-PKB in lung tissue by immunohistochemistry and the activity change of PI3K/PKB signal pathway by protein blot (Western Blot) assay were detected. The relative data mentioned as above also detected in SO group after 12h. Results 3h after molding with the p-PKB activity gradually increased, ICAM-1 expression increased, which were positively correlated (r=0.772, P<0.05); Western Blot test results shows that the PI3K/PKB signaling pathway is activated
引文
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