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巨噬细胞移动抑制因子对早期急性胰腺炎的影响

[Effects of macrophage migration inhibitory factor on early acute pancreatitis].

作者信息

Zhu Zhiqiang, Zheng Xiangyu, Zhang Luanluan, Zhang Yepeng, Mao Yujing, Zhu Changju

机构信息

Department of Emergency Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan, China. Corresponding author: Zhu Changju, Email:

出版信息

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020 Feb;32(2):221-225. doi: 10.3760/cma.j.cn121430-20200113-00041.

Abstract

OBJECTIVE

To investigate the value of macrophage migration inhibitor factor (MIF) in early severe acute pancreatitis (SAP).

METHODS

(1) Animal 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). (2) Clinical 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 evaluation II (APACHE II) 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.

RESULTS

(1) The 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): 2 862.79±238.33 vs. 1 728.32±197.59, liver MIF (ng/L): 2 141.39±328.07 vs. 1 372.70±163.41, pancreas MIF (ng/L): 4 468.00±1 324.31 vs. 1 572.06±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. (2) Clinical 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; APACHE II scores 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 APACHE II scores 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).

CONCLUSIONS

MIF can predict the occurrence of early SAP, and it is related to the severity of early AP.

摘要

目的

探讨巨噬细胞移动抑制因子(MIF)在早期重症急性胰腺炎(SAP)中的作用。

方法

(1)动物实验:采用随机数字表法,将24只雄性Sprague-Dawley(SD)大鼠分为假手术组、SAP 3小时组、6小时组和12小时组,每组6只。通过逆行胆胰管注射5%牛磺胆酸钠制备SAP大鼠模型。于造模后3、6和12小时采集肝、肾、肺、胰腺组织及血清样本。假手术组在翻动胰腺后立即采集组织和血清。苏木精-伊红(HE)染色显微镜下观察胰腺组织病理学变化。采用酶联免疫吸附测定(ELISA)法检测血清、肝、肾、肺及胰腺组织中MIF水平。(2)临床研究:进行一项观察性研究。选取2018年12月至2019年10月在郑州大学第一附属医院急诊科就诊的72例腹痛发作24小时内(血淀粉酶高于正常上限3倍)且临床诊断符合急性胰腺炎(AP)标准的成年患者。采集静脉血,采用ELISA法测定血清MIF水平。记录24小时急性生理与慢性健康状况评分系统II(APACHE II)评分。根据修订的亚特兰大标准将患者分为SAP组(17例)、中度重症急性胰腺炎(MSAP)组(25例)和轻度急性胰腺炎(MAP)组(30例),进行组间比较。

结果

(1)动物实验结果显示,SAP组大鼠血清、肝及胰腺组织中MIF水平在造模后6小时均达峰值,与假手术组比较差异有统计学意义[血清MIF(ng/L):2 862.79±238.33比1 728.32±197.59,肝MIF(ng/L):2 141.39±328.07比1 372.70±163.41,胰腺MIF(ng/L):4 468.00±1 324.31比1 572.06±108.40,均P<0.01];造模后12小时血清、肝及胰腺组织中MIF水平虽有所下降,但仍显著高于假手术组。然而,造模后3、6和12小时,SAP大鼠肺和肾组织中MIF水平与假手术组比较差异无统计学意义。(2)临床观察显示,SAP、MSAP及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)和(7.21±2.47)μg/L;APACHE II评分也依次降低,分别为10.41±3.74、7.60±3.18和4.00±2.41。相关性分析显示,SAP、MSAP及MAP患者血清MIF水平与各自组APACHE II评分呈良好相关性,表明MIF水平与疾病严重程度呈正相关(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严重程度相关。

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