急性胰腺炎大鼠不同病情程度Notch-1信号表达特征探讨
|
摘要
目的探讨急性胰腺炎大鼠不同病情程度Notch-1信号表达特征。方法选取60只雄性成年SD大鼠进行研究,注射浓度不同的牛磺胆酸钠(浓度分别为3%与0. 5%),剂量为1 m L/kg,注射速度为0. 06 m L/min,建重症、轻型急性胰腺炎大鼠模型各30只,经PCR逆转录反应法测定Notch-1在重症、轻型急性胰腺炎大鼠中的表达水平,明确其表达量峰值。绘制受试者工作特征曲线(ROC)分析Notch-1 mRNA表达量峰值对重症急性胰腺炎(severe acute pancreatitis,SAP)的预测价值。在建模成功后采集3 m L血样,测定血清白介素-6(interleukin-6,IL-6)、白介素1β(interleukin-1β,IL-1β)水平,分析SAP大鼠Notch-1mRNA表达量峰值与IL-6、IL-1β的相关性。结果重症组术后4 h、6 h、8 h、24 h、48 h的Notch-1 mRNA表达量显著高于轻型组(P <0. 05)。Notch-1 mRNA峰值预测SAP的曲线下面积为0. 674(标准误=0. 070,P=0. 021,95%CI=0. 536～0. 812)。重症组血清IL-6、IL-1β高于轻型组,差异有统计学意义(P <0. 05)。Pearson线性相关分析提示Notch-1 mRNA峰值与IL-6、IL-1β呈正相关(r=0. 588、0. 696,均P <0. 05)。结论与轻型急性胰腺炎相比,重症患者的Notch-1 mRNA表达量明显增高,且其峰值与SAP大鼠血清IL-6、IL-1β水平有相关性。
Objective To investigate the expression characteristics of Notch-1 signal in rats with acute pancreatitis. Methods 60 adult male SD rats were injected with different concentrations of sodium taurocholate( 3% and 0. 5%, respectively), at a dose of 1 mL/kg and a injection rate of 0. 06 mL/min. Thirty rats with severe and mild acute pancreatitis were established. The expression level of Notch-1 in rats with severe and mild acute pancreatitis was determined by RT-PCR, and the peak value of Notch-1 expression was determined. Predictive value of Notch-1 mRNA peak expression in SAP by receiver operating curve( ROC). After successful modeling, 3 mL blood samples were collected and serum levels of interleukin-6( IL-6) and interleukin-1β( IL-1β) were measured. Analysis of the correlation between Notch-1 expression peak and IL-6, IL-1 beta in SAP rats. Results The expression of NOTCH-1 in severe group was significantly higher than that in light group at 4, 6, 8, 24 and 48 hours after operation( P < 0. 05). The area under the curve of Notch-1 mRNA peak predicted SA P was 0. 674( standard error = 0. 070, P = 0. 021, 95% CI = 0. 536 ～ 0. 812). The serum levels of IL-6 and IL-1 beta in severe group were higher than those in light group( P < 0. 05). Pearson linear correlation analysis showed that Notch-1 gene peak was positively correlated with IL-6 and IL-1β( r = 0. 588、0. 696, P < 0. 05). Conclusion Compared with mild acute pancreatitis, Notch-1 expression in severe patients was significantly increased, and its peak value was correlated with serum levels of IL-6 and IL-1 beta in SAP rats.
Objective To investigate the expression characteristics of Notch-1 signal in rats with acute pancreatitis. Methods 60 adult male SD rats were injected with different concentrations of sodium taurocholate( 3% and 0. 5%, respectively), at a dose of 1 mL/kg and a injection rate of 0. 06 mL/min. Thirty rats with severe and mild acute pancreatitis were established. The expression level of Notch-1 in rats with severe and mild acute pancreatitis was determined by RT-PCR, and the peak value of Notch-1 expression was determined. Predictive value of Notch-1 mRNA peak expression in SAP by receiver operating curve( ROC). After successful modeling, 3 mL blood samples were collected and serum levels of interleukin-6( IL-6) and interleukin-1β( IL-1β) were measured. Analysis of the correlation between Notch-1 expression peak and IL-6, IL-1 beta in SAP rats. Results The expression of NOTCH-1 in severe group was significantly higher than that in light group at 4, 6, 8, 24 and 48 hours after operation( P < 0. 05). The area under the curve of Notch-1 mRNA peak predicted SA P was 0. 674( standard error = 0. 070, P = 0. 021, 95% CI = 0. 536 ～ 0. 812). The serum levels of IL-6 and IL-1 beta in severe group were higher than those in light group( P < 0. 05). Pearson linear correlation analysis showed that Notch-1 gene peak was positively correlated with IL-6 and IL-1β( r = 0. 588、0. 696, P < 0. 05). Conclusion Compared with mild acute pancreatitis, Notch-1 expression in severe patients was significantly increased, and its peak value was correlated with serum levels of IL-6 and IL-1 beta in SAP rats.
引文
[1]郑亚民,周震,高崇崇,等.急性重症胰腺炎早期死亡的风险因素分析[J].中国医药导报,2017,14(13):61-64.
[2]张露,王玮.重症急性胰腺炎患者早期危险因素分析以及对预后的影响[J].现代消化及介入诊疗,2016,21(6):822-824.
[3]Deftos M L,He Y W,Ojala E W,et al.Correlating notch signaling with thymocyte maturation[J].Immunity,2016,9(6):777-786.
[4]卢晓玉.Numb蛋白及Numb/Notch信号通路对人胰腺癌细胞株放疗敏感性的影响[J].癌症进展,2018,16(2):159-162.
[5]王红卫,赵阳,李鹏,等.Notch1对人胰腺癌细胞迁移及侵袭能力影响的体外实验研究[J].新疆医科大学学报,2017,40(12):1559-1563.
[6]杨波,黄鹤光,陈大良,等.逆行性胰胆管注射法制作重症急性胰腺炎大鼠模型[J].福建医科大学学报,2002,36(1):71-72.
[7]伍迪,朱责梅,杨丝丝,等.Notch信号:一个新型代谢调节因子[J].生理科学进展,2016,47(6):459-463.
[8]刘刚,张磊,扶世杰.Notch信号通路在软骨细胞分化过程中的作用[J].医学研究生学报,2016,29(10):1111-1115.
[9]邹礼梁,王奎,满夏楠,等.Notch信号通路在中枢神经系统神经发生过程中作用的研究进展[J].中国康复理论与实践,2016,22(11):1281-1284.
[10]种莉,唐鹏,刘鹏,等.Notch通路对缺氧诱导N9小胶质细胞释放炎症因子的调节作用[J].中华神经医学杂志,2015,14(7):678-683.
[11]李红蓉,孙颖,常成成,等.Notch信号通路调节巨噬细胞极化研究进展[J].医学研究生学报,2015,28(12):1316-1321.
[12]郭敏,余鹏飞,白槟,等.细胞凋亡通路在小鼠酒精性胰腺炎发展过程中的作用[J].中华胰腺病杂志,2017,17(17):35-39.
[13]李淑静,张爱东,袁博,等.舒尼替尼通过抑制Notch-1表达诱导人胰腺癌细胞凋亡[J].实用医学杂志,2018,34(14):2303-2306.
[14]李冰,熊正方,郭亚民.长链非编码RNA ROR通过notch1蛋白调控胰腺癌细胞的增殖凋亡[J].实用医学杂志,2017,33(12):30-35.
[15]易超,苏雅婷,丁伟,等.Notch受体在胰腺癌组织中的表达及其临床意义[J].现代生物医学进展,2016,16(34):6684-6687.
[16]彭艳,文刚,彭雪刚,等.重症胰腺炎患者血淀粉酶、TNF-α、IL-1β和PCT在CRRT治疗后的变化和意义[J].标记免疫分析与临床,2017,24(9):1011-1014.
[17]李劲松,雷元辉,陈继军.连续性静脉-静脉血液滤过对重症胰腺炎患者血清内毒素、TNF-α、IL-1β、CRP水平的影响[J].中国临床研究,2016,29(3):328-330.
[18]Chi D Z,Chen J,Huang D P.Influence of interleukin-1βand interleukin-6 gene polymorphisms on the development of acute pancreatitis.[J].Genetics&Molecular Research Gmr,2015,14(1):975-80.
[19]Xu C,Shen J,Zhang J,et al.Recombinant interleukin-1 receptor antagonist attenuates the severity of chronic pancreatitis induced by TNBS in rats.[J].Biochemical Pharmacology,2015,93(4):449-460.
[20]王丽芳,张朋伟,李云婷,等.重症急性胰腺炎患者血清IL-17、IL-17R、IL-6、HMGB1和IL-10水平变化及临床意义[J].中国卫生检验杂志,2016,26(16):2334-2335.
[21]闫长孟,田桦,霍明霞,等.β-胡萝卜素对急性胰腺炎大鼠NF-κB、TGF-β1及IL-6表达的影响[J].江苏医药,2018,44(4):357-360.
[22]卓越,邱小松,薛婷,等.IL-6、IL-10联合BISAP评分在重症急性胰腺炎预后评估中的作用研究[J].现代生物医学进展,2017,17(29):118-121.
[23]唐凯玲,龙鼎新.Notch信号通路在相关疾病中的研究进展[J].中南医学科学杂志,2016,44(2):219-223.
[24]石乔,王卫星.胰腺腺泡细胞和胰岛β细胞损伤修复及再生的研究进展[J].微循环学杂志,2017,27(1):60-64.
[25]石占利,孙静,李志会,等.细胞凋亡在重症急性胰腺炎并发急性肺损伤中的作用机制[J].解放军医学杂志,2017,42(11):48-52.
[2]张露,王玮.重症急性胰腺炎患者早期危险因素分析以及对预后的影响[J].现代消化及介入诊疗,2016,21(6):822-824.
[3]Deftos M L,He Y W,Ojala E W,et al.Correlating notch signaling with thymocyte maturation[J].Immunity,2016,9(6):777-786.
[4]卢晓玉.Numb蛋白及Numb/Notch信号通路对人胰腺癌细胞株放疗敏感性的影响[J].癌症进展,2018,16(2):159-162.
[5]王红卫,赵阳,李鹏,等.Notch1对人胰腺癌细胞迁移及侵袭能力影响的体外实验研究[J].新疆医科大学学报,2017,40(12):1559-1563.
[6]杨波,黄鹤光,陈大良,等.逆行性胰胆管注射法制作重症急性胰腺炎大鼠模型[J].福建医科大学学报,2002,36(1):71-72.
[7]伍迪,朱责梅,杨丝丝,等.Notch信号:一个新型代谢调节因子[J].生理科学进展,2016,47(6):459-463.
[8]刘刚,张磊,扶世杰.Notch信号通路在软骨细胞分化过程中的作用[J].医学研究生学报,2016,29(10):1111-1115.
[9]邹礼梁,王奎,满夏楠,等.Notch信号通路在中枢神经系统神经发生过程中作用的研究进展[J].中国康复理论与实践,2016,22(11):1281-1284.
[10]种莉,唐鹏,刘鹏,等.Notch通路对缺氧诱导N9小胶质细胞释放炎症因子的调节作用[J].中华神经医学杂志,2015,14(7):678-683.
[11]李红蓉,孙颖,常成成,等.Notch信号通路调节巨噬细胞极化研究进展[J].医学研究生学报,2015,28(12):1316-1321.
[12]郭敏,余鹏飞,白槟,等.细胞凋亡通路在小鼠酒精性胰腺炎发展过程中的作用[J].中华胰腺病杂志,2017,17(17):35-39.
[13]李淑静,张爱东,袁博,等.舒尼替尼通过抑制Notch-1表达诱导人胰腺癌细胞凋亡[J].实用医学杂志,2018,34(14):2303-2306.
[14]李冰,熊正方,郭亚民.长链非编码RNA ROR通过notch1蛋白调控胰腺癌细胞的增殖凋亡[J].实用医学杂志,2017,33(12):30-35.
[15]易超,苏雅婷,丁伟,等.Notch受体在胰腺癌组织中的表达及其临床意义[J].现代生物医学进展,2016,16(34):6684-6687.
[16]彭艳,文刚,彭雪刚,等.重症胰腺炎患者血淀粉酶、TNF-α、IL-1β和PCT在CRRT治疗后的变化和意义[J].标记免疫分析与临床,2017,24(9):1011-1014.
[17]李劲松,雷元辉,陈继军.连续性静脉-静脉血液滤过对重症胰腺炎患者血清内毒素、TNF-α、IL-1β、CRP水平的影响[J].中国临床研究,2016,29(3):328-330.
[18]Chi D Z,Chen J,Huang D P.Influence of interleukin-1βand interleukin-6 gene polymorphisms on the development of acute pancreatitis.[J].Genetics&Molecular Research Gmr,2015,14(1):975-80.
[19]Xu C,Shen J,Zhang J,et al.Recombinant interleukin-1 receptor antagonist attenuates the severity of chronic pancreatitis induced by TNBS in rats.[J].Biochemical Pharmacology,2015,93(4):449-460.
[20]王丽芳,张朋伟,李云婷,等.重症急性胰腺炎患者血清IL-17、IL-17R、IL-6、HMGB1和IL-10水平变化及临床意义[J].中国卫生检验杂志,2016,26(16):2334-2335.
[21]闫长孟,田桦,霍明霞,等.β-胡萝卜素对急性胰腺炎大鼠NF-κB、TGF-β1及IL-6表达的影响[J].江苏医药,2018,44(4):357-360.
[22]卓越,邱小松,薛婷,等.IL-6、IL-10联合BISAP评分在重症急性胰腺炎预后评估中的作用研究[J].现代生物医学进展,2017,17(29):118-121.
[23]唐凯玲,龙鼎新.Notch信号通路在相关疾病中的研究进展[J].中南医学科学杂志,2016,44(2):219-223.
[24]石乔,王卫星.胰腺腺泡细胞和胰岛β细胞损伤修复及再生的研究进展[J].微循环学杂志,2017,27(1):60-64.
[25]石占利,孙静,李志会,等.细胞凋亡在重症急性胰腺炎并发急性肺损伤中的作用机制[J].解放军医学杂志,2017,42(11):48-52.