HBx基因突变及PLA_(2)R表达在乙肝相关膜性肾病中的作用  

Effect of HBx gene mutation on PLA_(2)R positive HBV associated membranous nephropathy

作　　者：蒋伟[1] 董晖[1] 孙静宜 卜泉东[1] 赵龙[1] 王雁飞[1] 车琳 徐岩[1] Jiang Wei;Dong Hui;Sun Jingyi;Bu Quandong;Zhao Long;Wang Yanfei;Che Lin;Xu Yan(Department of Nephrology,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院肾内科,266003

出　　处：《中华实验和临床病毒学杂志》2021年第1期39-43,共5页Chinese Journal of Experimental and Clinical Virology

基　　金：国家自然科学基金(81870494);山东省卫健委(2015WS0341);青岛市医疗卫生优秀人才培养项目(2020-2022);中华医学会临床医学科研专项(20010080800)。

摘　　要：目的探讨乙型肝炎病毒(HBV)X基因突变在乙肝相关性膜性肾病(HBV-MN)M型磷脂酶2受体(PLA_(2)R)表达以及可能的致病机制研究。方法由肾穿刺活检证实的HBV-MN的患者103例,根据肾组织PLA2R免疫荧光检测结果分为2组,PLA_(2)R阳性组66例,PLA_(2)R阴性组37例。采用t检验比较两组间的临床生化指标;根据HBV-MN病理分期的不同,MNⅠ期(病理损伤较轻)和MNII-Ⅲ期(病理损伤重),采用One-way ANOVA单因素方差分析比较两组间肾脏病理损伤;Spearman相关分析比较PLA_(2)R表达强度与肾脏病理损伤的差别;最后分析两组患者HBx基因突变位点。结果两组患者24 h尿蛋白定量差别具有统计学意义(t=2.803,P=0.006);而血白蛋白水平(t=-0.313,P=0.755)、血肌酐(t=-0.332,P=0.741)、胆固醇(t=0.312,P=0.756)、补体C3(t=0.589,P=0.557)差别无统计学意义。MNⅠ期在两组所占比例差别具有统计学意义(X^(2)=7.449,P=0.006);MNII-Ⅲ期两组差别同样具有统计学意义(X^(2)=10.15,P=0.034);其次,将PLA_(2)R阳性组根据不同PLA_(2)R荧光染色强度与不同MN病理分期行Spearman相关性分析,差别具有统计学意义(r=0.325,P=0.008)。最后,分析两组间HBx基因序列突变,发现nt1753位点突变可能与PLA2R表达相关。结论研究中2/3的HBV-MN患者存在肾组织PLA_(2)R阳性表达,PLA_(2)R阳性组患者伴有尿蛋白排泄量增多以及肾脏病理损伤加重;同时,HBx基因中nt1753位点突变与PLA2R的表达相关,可能是PLA_(2)R阳性HBV-MN重要的发病机制。Objective To investigate the expression of HBV X,gene mutation in M type phospholipase 2 receptor(PLA_(2)R)in hepatitis B associated membranous nephropathy(HBV-MN)and its possible pathogenesis.Methods According to the result of PLA_(2)R immunofluorescence detection in renal tissue,103 patients with HBV-MN confirmed by renal biopsies were divided into two groups:PLA_(2)R positive group(n=66)and PLA_(2)R negative group(n=37).T test was used to compare the clinical biochemical measurements between the two groups.According to MN I stages(mild pathological injury)and MN II-III stage(severe pathological injury)of HBV-MN pathological stage,One-way ANOVA analysis was used to compare the pathological injury of kidney between the two groups.Spearman correlation analysis was used to compare the expression intensity of PLA_(2)R and pathological injury of kidney.Finally,the mutation sites of HBx gene in the two groups were analyzed.Results There was significant difference in 24 h urinary protein between the two groups(t=2.803,P=0.006).However,there was no significant difference in serum albumin level(t=-0.313,P=0.755),serum creatinine(t=-0.332,P=0.741),cholesterol(t=0.312,P=0.756)and complement C3(t=0.589,P=0.557)between the two groups.There was significant difference between the two groups in MN stage I(X^(2)=7.449,P=0.006)and MN stage II-III(X^(2)=10.15,P=0.034).Secondly,the correlation analysis of Spearman between PLA_(2)R staining intensity and different MN pathological stages was statistically significant(r=0.325,P=0.008).Finally,the mutation of HBx gene sequence between the two groups was analyzed,and it was found that the mutation at nt1753 site might be related to the expression of PLA_(2)R.Conclusions The positive expression of PLA_(2)R in renal tissue was found in 2/3 HBV-MN patients.The PLA_(2)R positive group was accompanied by the increase of urinary protein excretion and the aggravation of renal pathological injury.At the same time,nt1753 site mutations in HBx gene are related to the expression of PLA_(2)R,which

关 键 词：乙肝相关膜性肾病 M型磷脂酶2受体 X基因 突变 

分 类 号：R512.62[医药卫生—内科学] R692[医药卫生—临床医学]