摘要
目的检测CP合并外分泌功能不全(PEI)患者外周血单核细胞(PBMC)核心生物钟基因mRNA表达量及血清生物钟紊乱相关蛋白水平,探讨其临床诊断价值。方法收集2015年1月至2022年1月间上海市第一人民医院确诊的68例CP患者外周血标本以及临床相关资料,并以30名健康体检者外周血作为对照组。CP临床分期参照M-ANNHEIM分类系统。采用实时荧光定量PCR法检测PBMC核心生物钟基因Clock,Bmal1,Per1、2、3,Cry1、2 mRNA表达量,采用ELISA法检测外周血清生物钟紊乱相关蛋白TrkB、CD_(36)和Rbp水平。绘制差异表达指标的受试者工作特征曲线(ROC),计算曲线下面积(AUC),评估其诊断PEI的效能。结果CP患者PBMC Per1 mRNA表达量较对照组显著降低(0.76比1,P<0.05),其诊断PEI的AUC值为0.744(95%CI0.628~0.860),临界值为0.72,灵敏度为84.8%,特异度为57.1%;血清CD_(36)蛋白水平较对照组显著升高[(33.85±19.74)ng/ml比(24.71±11.53)ng/ml,P<0.05],其诊断PEI的AUC值为0.834(95%CI0.735~0.932),临界值为29.75 pg/ml,灵敏度为74.3%,特异度为84.8%。CD_(36)表达随CP临床分期的增高而升高,Ⅰ、Ⅱ、Ⅲ期患者两两比较差异均有统计学意义(P值均<0.05);Ⅰ期患者PBMC Per1mRNA表达量显著高于Ⅱ期及Ⅲ期患者,差异有统计学意义(P<0.05),但Ⅱ期与Ⅲ期患者差异无统计学意义。结论PBMC Per1mRNA表达量下降及血清CD_(36)升高与CP并发PEI显著相关,对PEI的诊断及指导相关临床实践具有潜在价值。
Objective To examine the expression of core clock genes in the peripheral blood mononuclear cells(PBMCs)and the level of circadian disturbance-related proteins in the serum of chronic pancreatitis(CP)patients with pancreatic exocrine insufficiency(PEI),and explore their potential diagnostic value in clinical practice.Methods The peripheral blood samples and related clinical data from 68 patients diagnosed with CP in Shanghai General Hospital from Jan 2015 to Jan 2022 were collected.Peripheral blood samples from 30 healthy individuals were used for control.The M-ANNHEIM classification system was used to stratify the clinical stages of patients with CP.The mRNA expression of the core clock genes,including Clock,Bmal1,Per1/2/3 and Cry1/2 in PBMCs was analyzed using realtime qPCR,and the expression of circadian disturbance-related proteins like TrkB,CD_(36) and Rbp in serum was measured with ELISA.The receiver operating characteristic curve(ROC)and the area under curve(AUC)was used to test the efficiency for diagnozing PEI.Results The mRNA expression of Per1 in CP patients was significantly decreased(0.76 vs 1,P<0.05),and the AUC for diagnozing PEI was 0.744(95%CI 0.628-0.860),with a cut-off value of 0.72;and the sensitivity and specificity was 84.8%and 57.1%,respectively.The protein abundance of serum CD_(36) was significantly increased in CP patients(33.85±19.74ng/ml vs 24.71±11.53 ng/ml,P<0.05);the AUC for diagnozing PEI was 0.834(95%CI 0.735-0.932),with a cut-off value of 29.75 pg/ml;and the sensitivity and specificity was 74.3%and 84.8%,respectively.The expression of CD_(36) was increased with the increase of CP clinical stage,and there were statistically significant differences between either two stages(all P value<0.05).The mRNA expression of Per1 in patients with CP in StageⅠwas significantly higher than that in patients with CP in StageⅡorⅢ,and the differences were statistically significant(P<0.05),but no statistical difference was found between StageⅡand StageⅢ.Conclusions The decreased expressi
作者
蒋巍亮
程志远
沈施恩
王传阳
陈佳惠
冯赟
王伟
万荣
Jiang Weiliang;Cheng Zhiyuan;Shen Shien;Wang Chuanyang;Chen Jiahui;Feng Yun;Wang Wei;Wan Rong(Department of Gastroenterology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Key Laboratory of Pancreatic Disease,Shanghai 200080,China)
出处
《中华胰腺病杂志》
CAS
2023年第1期15-19,共5页
Chinese Journal of Pancreatology
基金
上海交通大学多学科交叉培育项目(YG2021QN92)。
关键词
生物钟
胰腺炎
慢性
胰腺外分泌功能不全
Circadian clocks
Pancreatitis,chronic
Exocrine pancreatic insufficiency
