非酒精性脂肪性肝病患者血清claudin-1、claudin-4的变化及其与病情程度的相关性

Changes in serum levels of claudin-1 and claudin-4 in patients with nonalcoholic fatty liver disease:Association with disease severity

目的观察非酒精性脂肪性肝病患者血清闭锁蛋白1(claudin-1)和闭锁蛋白4(claudin-4)的变化,分析其与肠道黏膜屏障功能及病情程度的关系.方法选取79例非酒精性脂肪性肝病患者,按病情程度分为轻度(n=23)、中度(n=27)、重度(n=29),采用ELISA法测定其血清二胺氧化酶(diamine oxidase,DAO)、内毒素(endotoxin,ET)及血清claudin-1及claudin-4含量,并选取同期健康体检者40例作为对照.结果与对照组比较,患者组血清DAO、ET及claudin-4含量均明显升高(P<0.01,P<0.05),而血清claudin-1含量则显著上升(P<0.01).患者组血清DAO、ET及claudin-4含量随着病情程度的加重呈上升趋势,而血清claudin-1含量出现下降趋势.重度患者血清DAO、ET及claudin-4含量较轻中度患者明显上升(P<0.01,P<0.05);血清claudin-1含量则较轻中度患者明显下降(P<0.01,P<0.05).相关性分析表明,血清claudin-1含量与血清DAO、ET含量、病情程度呈明显负相关(r=-0.695、-0.738、-0.741,P<0.01);claudin-4含量与血清DAO、ET含量、病情程度呈明显正相关(r=0.779、0.755、0.875,P<0.01).结论非酒精性脂肪性肝病患者存在明显的肠黏膜功能障碍,且与其病情程度密切相关;肠黏膜紧密连接蛋白claudin-1、claudin-4表达异常可能是发生肠黏膜功能障碍的重要机制.

AIM To investigate the changes in serum levels of claudin-1 and claudin-4 in patients with nonalcoholic fatty liver disease （NAFLD） and to analyze their relationship with disease severity and intestinal barrier function. METHODS Seventy-nine patients with NAFLD were divided into a mild group （n = 23）, a moderate group （n = 27）, and a severe group （n = 29） according to disease severity. The levels of serum claudin-1, claudin-4, diamine oxidase （DAO） and endotoxin （ET） were detected by ELISA. Forty healthy people were included as a health control group. RESULTS The levels of serum claudin-4, DAO and ET increased significantly, but the level of serum claudin-1 decreased significantly in patients with NAFLD than in the control group （P 〈 0.01, P 〈 0.05）. The levels of serum claudin-4, DAO and ET showed a rising trend and the levels of serum claudin-1 showed a downward trend with the aggravation of disease. The levels of serum claudin-4, DAO and ET increased significantly, but the level of serum claudin-1 decreased significantly in the severe group than in the mild group and moderate group （P 〈 0.01, P 〈 0.05）. There was a significant negative correlation between serum claudin-1 and serum DAO, ET and disease severity （r = -0.695, -0.738, -0.741, P 〈 0.01）, but there was a significant positivecorrelation between serum claudin-4, DAO and ET and disease severity （r = 0.779, 0.755, 0.875, P 〈 0.01）. CONCLUSION Patients with NAFLD have intestinal mucosal barrier dysfunction, which is closely related with disease severity. Abnormal expression of the claudin-1 and claudin-4 proteins may be molecular mechanisms of intestinal mucosal barrier dysfunction.