外源性Apelin-13对重症急性胰腺炎大鼠治疗作用及其机制研究
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摘要
目的:探究NO在重症急性胰腺炎(SAP)损伤中的作用机制,并明确外源性Apelin-13对SAP的治疗效果。方法:通过开腹胰胆管注射5%牛磺胆酸钠制作SAP大鼠模型。应用随机数表法将60只SPF级SD大鼠随机分三组,每组20只,分别为空白组、SAP组、治疗组。其中空白组分离胃十二指肠,找到胰胆管,不做其他处理;SAP组及治疗组按照SAP动物模型制作标准进行,治疗组在造模同时通过尾静脉注射外源性Apelin-13,SAP组给予注射等量生理盐水。分别于造模后3、6、12、24、48h采集下腔静脉血同时取其胰腺组织。通过ELISA法检测大鼠血清AMS、IL-6、TNF-α、NO浓度,通过蛋白免疫印记检测胰腺组织iNOS、eNOS表达情况,胰腺组织HE染色明确胰腺组织病理损伤。结果:同一观察点治疗组与空白组相比,AMS、IL-6、TNF-α、NO均增高(P<0.05),iNOS呈高表达、eNOS则呈现低表达(P<0.05),胰腺组织损伤较明显。同一观察点SAP组与空白组相比,AMS、IL-6、TNF-α、NO均明显增高(P<0.05),iNOS呈高表达、eNOS则呈现低表达(P<0.05),胰腺组织损伤更显著。同一观察点治疗组与SAP组相比,血清淀粉酶、IL-6、TNF-α、NO均降低(P<0.05),iNOS呈低表达、eNOS则呈现高表达(P<0.05),胰腺组织损伤较轻。结论:外源性Apelin-13对大鼠重症急性胰腺炎的治疗有较明显效果,其机制可能是通过上调eNOS表达、下调iNOS表达从而调节体内NO含量。
Objective:To explore the mechanism of action of NO in SAP injury and to determine the therapeutic effect of exogenous Apelin-13 on SAP.Methods:SAP rat model was made by injecting 5% sodium taurocholate into open pancreaticobiliary ducts.60 SPF-grade SD rats were randomly divided into 3 groups using random number table,20 in each group,namely blank group,SAP group and treatment group.The blank group separated the gastroduodenum and found the pancreaticobiliary tube,and no other treatment was performed.The SAP group and the treatment group were performed according to the SAP animal model.The treatment group was injected with exogenous Apelin-13 through the tail vein.The SAP group was given an injection of the same amount of physiological saline.At the same time,3,6,12,24 and 48 hafter modeling,the inferior vena cava blood was collected and the pancreatic tissue was taken.The concentration of AMS,IL-6,TN F-αand NO in rats serum were detected by ELISA.The expression of iNOS and eNOS in pancreas was detected by Western blot.Histopathological lesions of pancreas were confirmed by HE staining.Results:Compared with the blank group,AMS,IL-6,TNF-αand NO in treatment group were all increased in the same observation point(P<0.05),iNOS was highly expressed,and eNOS was lowly expressed(P<0.05).The damage was obvious.At the same observation point,compared with the blank group,the SAP group had significantly higher AMS,IL-6,TNF-αand NO(P<0.05),high iNOS expression,and low eNOS expression(P<0.05).Damage was more pronounced.The treatment group compared with SAP group,AMS,IL-6,TNF-αand NO were decreased in the same observation group(P<0.05),iNOS was low,and eNOS was high(P<0.05).The damage is lighter.Conclusion:Exogenous Apelin-13 has a significant effect on the treatment of severe acute pancreatitis in rats.The mechanism may beto up-regulate the expression of eNOS and downregulate the expression of iNOS to regulate NO content in vivo.
Objective:To explore the mechanism of action of NO in SAP injury and to determine the therapeutic effect of exogenous Apelin-13 on SAP.Methods:SAP rat model was made by injecting 5% sodium taurocholate into open pancreaticobiliary ducts.60 SPF-grade SD rats were randomly divided into 3 groups using random number table,20 in each group,namely blank group,SAP group and treatment group.The blank group separated the gastroduodenum and found the pancreaticobiliary tube,and no other treatment was performed.The SAP group and the treatment group were performed according to the SAP animal model.The treatment group was injected with exogenous Apelin-13 through the tail vein.The SAP group was given an injection of the same amount of physiological saline.At the same time,3,6,12,24 and 48 hafter modeling,the inferior vena cava blood was collected and the pancreatic tissue was taken.The concentration of AMS,IL-6,TN F-αand NO in rats serum were detected by ELISA.The expression of iNOS and eNOS in pancreas was detected by Western blot.Histopathological lesions of pancreas were confirmed by HE staining.Results:Compared with the blank group,AMS,IL-6,TNF-αand NO in treatment group were all increased in the same observation point(P<0.05),iNOS was highly expressed,and eNOS was lowly expressed(P<0.05).The damage was obvious.At the same observation point,compared with the blank group,the SAP group had significantly higher AMS,IL-6,TNF-αand NO(P<0.05),high iNOS expression,and low eNOS expression(P<0.05).Damage was more pronounced.The treatment group compared with SAP group,AMS,IL-6,TNF-αand NO were decreased in the same observation group(P<0.05),iNOS was low,and eNOS was high(P<0.05).The damage is lighter.Conclusion:Exogenous Apelin-13 has a significant effect on the treatment of severe acute pancreatitis in rats.The mechanism may beto up-regulate the expression of eNOS and downregulate the expression of iNOS to regulate NO content in vivo.
引文
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[12]叶广森,陈湛生,王莉.活性氧簇和一氧化氮在预测胰腺炎患者病情变化中的意义[J].内科,2018,13(3):391-393.
[2]陈明勋,刘东亮,罗磊,等.大黄红藤消炎方治疗重症急性胰腺炎临床疗效及对PCT、sICAM-1影响分析[J].陕西中医,2018,39(9):1217-1220.
[3]Kleinz MJ,Davenport AP.Emerging roles of apelin in biology and medicine[J].Pharmacol Ther,2005,107(2):198-211.
[4]符婉,田绍文,游咏,Apelin-13最新研究进展[J].天津医药,2014,42(11):1138-1140.
[5]白槟,徐斌,刘朝旭,等.逆行胰胆管注射牛磺胆酸钠诱导重症急性胰腺炎模型多器官损害观察[J].科学技术与工程,2013,13(15):4141-4147.
[6]陈翠连,王明林,袁启奎,等.常见生化指标联合检测对急性胰腺炎病情严重程度的评估价值[J].重庆医学,2017,46(31):4402-4404.
[7]Sternby H,Hartman H,Johansen D,et al.Predictive Capacity of Biomarkers for Severe Acute Pancreatitis[J].Eur Surg Res,2016,56(3-4):154-163.
[8]连凌云,李前进,杨和平,等.区域动脉灌注乌司他丁与血液净化及其二者联合治疗重症胰腺炎临床比较[J].陕西医学杂志,2017,46(11):1581-1583.
[9]Xu P,Wang J,Yang ZW,et al.Regulatory roles of the PI3K/Akt signaling pathway in rats with severe acute pancreatitis[J].PLoS One,2013,8(11):e81767.
[10]聂军.血清促炎细胞因子白介素-6与急性胰腺炎严重程度的相关性[J].世界华人消化杂志,2015,23(17):2816-2819.
[11]李昌,母珍珍,王磊,等.诱导型一氧化氮合酶(iN-OS)对重症急性胰腺炎时胰岛内分泌功能的影响[J].中外医疗,2017,36(17):42-43,46.
[12]叶广森,陈湛生,王莉.活性氧簇和一氧化氮在预测胰腺炎患者病情变化中的意义[J].内科,2018,13(3):391-393.