两种类型急性胰腺炎患者早期外周血Toll样受体4基因多态性分析  

Peripheral blood Toll-like receptor 4 gene polymorphism in patients with mild or moderately severe acute pancreatitis

作　　者：陈文亮[1] 武世荣[1] 段俊芳[2] 赵小龙[3] 郭波 李文龙[1] 贾彬[1] 苏继荣[1] Chen Wenliang;Wu Shirong;Duan Junfang;Zhao Xiaolong;Guo Bo;Li Wenlong;Jia Bin;Su Jirong(Department of General Surgery;Department of Intensive Medicine,The Second Affiliated Hospital of Shanxi Medical University,Taiyuan 030001,China;Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第二医院普通外科,太原030001 [2]山西医科大学第二医院重症医学科,太原030001 [3]山西医科大学,太原030001

出　　处：《中华临床医师杂志（电子版）》2017年第24期2480-2485,共6页Chinese Journal of Clinicians(Electronic Edition)

基　　金：山西省科技厅科技攻关项目(20130313018-3)

摘　　要：目的探讨Toll样受体4(TLR4)(896A> G)基因多态性、核因子-κB激活在两种类型急性胰腺炎(AP)患者中的差异。方法选取山西医科大学第二医院2013年1月至2015年12月AP患者52例,其中轻症急性胰腺炎(MAP)和中重症急性胰腺炎(MSAP)各26例。采用错配PCR-限制性片段长度多态性分析方法检测外周血中TLR4(896A> G)突变频率、流式细胞术检测核因子-κB激活。各组间血淀粉酶、尿淀粉酶、APACHEⅡ评分、MCTSI评分的比较采用t检验;NF-κB激活组间数据采用重复测量方差分析;TLR4(896A> G)频率比较采用χ2检验。结果与MAP组相比,MSAP组APACHEⅡ评分和MCTSI评分均显著升高[(8.2±3.1)分vs(4.6±1.8)分;(5.2±1.4)分vs(2.4±0.8)分],差异具有统计学意义(t=3.408,P=0.004;t=5.422,P=0.000);但血、尿淀粉酶两者间差异无统计学意义(P> 0.05)。各组外周血中性粒细胞、单核巨噬细胞NF-κB p65激活不同时间段之间差异有统计学意义(F=125.387,P <0.001),时间与组别之间存在交互效应(F=55.466,P <0.001),不同组别间差异有统计学意义(F=1126.191,P <0.001)。TLR4(-/+)(896A> G)等位基因频率,MAP组与对照组相比差异无统计学意义(OR=3.13,P=0.63),MSAP组与对照组比较,差异具有统计学意义(OR=10.67,P=0.03)。结论 TLR4错义突变(TLR4896A> G)和核因子-κB激活在不同类型AP患者具有明显差异。重视TLR4/NF-κB跨膜信号转导通路在AP发病中的作用,对临床诊断及治疗具有一定指导价值。ObjectiveTo compare the difference in Toll like receptor 4 （TLR4） gene polymorphism and nuclear factor-kappa B （NF-κB） activation in patients with acute pancreatitis （AP） of different severity. MethodsA total of 52 patients with AP treated at the Second Affiliated Hospital of Shanxi Medical University between January 2013 and December 2015 were collected and divided into either a mild acute pancreatitis （MAP） group （n=26） or a moderately severe acute pancreatitis （MSAP） group （n=26）. TLR4 （896A 〉 G） mutation was analyzed by mispairing PCR-restriction fragment-length polymorphism analysis technique. Flow cytometry was used for detecting NF-κB activation in peripheral blood. Serum amylase, urine amylase, APACHE Ⅱ score, and MCTSI score were compared by the t-test. NF-κB activation was compared by repeated measurement analysis of variance. The frequency of TLR4 （896A〉 G） was compared by means of χ2 test. ResultsAPACHE Ⅱ and MCTSI were significantly higher in the MSAP group [（8.2±3.1） vs（4.6±1.8）, t=3.408, P=0.004; （5.2±1.4） vs （2.4±0.8）, t=5.422, P 〈 0.001, respectively], but blood amylase and urine amylase were not statistically significant between the two groups of patients （P 〉 0.05）. NF-κB activation in each group was significantly different among different time points （F=125.387, P 〈 0.001）, and there was an interaction between time and group （F=55.466, P 〈 0.001）. NF-κB activation was statistically significant between the two groups （F=1126.191, P 〈 0.001）. Compared with the control group, the allele frequency of TLR4 （-/＋ ） （896A 〉 G） in the MAP group was not significantly different （11.5%, OR=3.13, P〉0.05）, but the allele frequency in the MSAP group was significantly higher （30.8%, OR=10.67, P〈0.05）. ConclusionTLR4 gene polymorphism and NF-κB activation are significantly different in AP of different severity, and therefore they have value for guiding clinical diagnosis and treatment.

关 键 词：TOLL样受体4 核因子-ΚB 流式细胞术 急性胰腺炎 限制性片断长度多态性 

分 类 号：R576[医药卫生—消化系统]