巨噬细胞迁移抑制因子与早期急性胰腺炎的关系研究

Effects of macrophage migration inhibitory factor on early acute pancreatitis

目的:探讨巨噬细胞迁移抑制因子(MIF)在早期重症急性胰腺炎(SAP)病情严重程度评估中的价值。方法:①动物实验:按随机数字表法将24只雄性SD大鼠分为假手术组(Sham组)及SAP 3、6、12 h组,每组6只。通过逆行胰胆管注射5%牛磺胆酸钠制备SAP大鼠模型,分别于制备后3、6、12 h处死大鼠取肝脏、肾脏、肺脏、胰腺组织及血清标本;Sham组仅翻动胰腺后立即取组织和血清。采用苏木素-伊红(HE)染色,镜下观察胰腺组织病理学改变;采用酶联免疫吸附试验(ELISA)测定血清、肝脏、肾脏、肺脏、胰腺组织MIF水平。②临床研究:采用观察性研究,选择2018年12月至2019年10月就诊于郑州大学第一附属医院急诊科腹部疼痛发作时24 h内(血淀粉酶为正常参考值上限3倍)的72例成人患者,临床诊断符合胰腺炎(AP)标准。抽取静脉血,采用ELISA法测定血清MIF水平;记录24 h内急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)。根据修订后亚特兰大(Atlanta)标准将患者分为SAP组(17例)、中重症急性胰腺炎(MSAP)组(25例)、轻症急性胰腺炎(MAP)组(30例),进行组间比较。结果:①动物实验结果显示,SAP组大鼠制模后血清、肝脏、胰腺MIF水平均于6 h达峰值,与Sham组相比差异均有统计学意义〔血清MIF(ng/L):2862.79±238.33比1728.32±197.59,肝脏MIF(ng/L):2141.39±328.07比1372.70±163.41,胰腺MIF(ng/L):4468.00±1324.31比1572.06±108.40,均P<0.01〕;制模后12 h血清、肝脏、胰腺MIF水平虽有下降,但仍显著高于Sham组。但SAP大鼠肺脏、肾脏MIF水平在制模后3、6、12 h与Sham组相比差异均无统计学意义。②临床观察显示,SAP、MSAP、MAP患者早期血清MIF水平依次降低,分别为(14.83±2.99)、(10.17±2.64)、(7.21±2.47)μg/L;APACHEⅡ评分也依次降低,分别为(10.41±3.74)、(7.60±3.18)、(4.00±2.41)分。相关性分析显示,SAP、MSAP、MAP患者血清MIF水平分别与相应组的APACHEⅡ评分有较好的相关性,表现为MIF水平与病情严重程度呈正相关(SAP:r=0.51,P=0.03;MSAP:r=0.45,P=0.02;MAP:r=0.45,P=0.01)。结论:MIF可预测早期SAP的发生,且与早期AP的严重程度有一定的相关性。

Objective To investigate the value of macrophage migration inhibitor factor(MIF)in early severe acute pancreatitis(SAP).Methods①Animal experiment:according to the random number table method,24 male Sprague-Dawley(SD)rats were divided into Sham group and SAP 3,6 and 12 hours groups,with 6 rats in each group.SAP rat model was prepared by injecting 5%sodium taurocholate via the retrograde cholangiopancreatic duct.Liver,kidney,lung,pancreas and serum samples were harvested after 3,6 and 12 hours.In the Sham group,tissue and serum were harvested immediately after pancreas was turned over.The histopathological changes of the pancreas were observed microscopically by hematoxylin-eosin(HE)staining.The MIF levels of serum,liver,kidney,lung and pancreas were measured by enzyme linked immunosorbent assay(ELISA).②Clinical study:an observational study was conducted.Seventy-two adult patients within 24 hours of the onset of abdominal pain(blood amylase was 3 times the normal level),and the clinical diagnosis met the criteria of acute pancreatitis(AP)admitted to the emergency department of the First Affiliated Hospital of Zhengzhou University from December 2018 to October 2019 were enrolled.Venous blood was extracted and serum MIF level was determined by ELISA.Acute physiology and chronic health evaluationⅡ(APACHEⅡ)was recorded for 24 hours.Patients were divided into SAP group(17 cases),moderate severe acute pancreatitis(MSAP)group(25 cases),and mild acute pancreatitis(MAP)group(30 cases)according to the revised Atlanta criteria for comparison between groups.Results①The results of animal experiments showed that the serum,liver,and pancreatic MIF levels of rats in the SAP group all reached the peak at 6 hours after modeling,and the differences were statistically significant compared with the Sham group[serum MIF(ng/L):2862.79±238.33 vs.1728.32±197.59,liver MIF(ng/L):2141.39±328.07 vs.1372.70±163.41,pancreas MIF(ng/L):4468.00±1324.31 vs.1572.06±108.40,all P<0.01];although the levels of MIF in serum,liver and pancreas decreased at 12 hours after modeling,they were still significantly higher than Sham group.However,there was no statistically significant difference in MIF levels of lung and kidney in SAP rats compared with Sham group at 3,6 and 12 hours after molding.②Clinical observation showed that early serum MIF levels of SAP,MSAP and MAP patients decreased in order,(14.83±2.99),(10.17±2.64),and(7.21±2.47)μg/L,respectively;APACHEⅡscores also decreased in order,10.41±3.74,7.60±3.18 and 4.00±2.41 respectively.Correlation analysis showed that serum MIF levels in patients with SAP,MSAP,and MAP had a good correlation with APACHEⅡscores of the respective groups,showing that MIF levels was positively correlated with disease severity(SAP:r=0.51,P=0.03;MSAP:r=0.45,P=0.02;MAP:r=0.45,P=0.01).Conclusion MIF can predict the occurrence of early SAP,and it is related to the severity of early AP.