HBx基因突变及PLA 2R表达在乙肝相关膜性肾病中的作用
Effect of HBx gene mutation on PLA 2R positive HBV associated membranous nephropathy
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 2R)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PLA 2R免疫荧光检测结果分为2组,PLA 2R阳性组66例,PLA 2R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 2R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( X2=7.449, P=0.006);MNII-Ⅲ期两组差别同样具有统计学意义( X2=10.15, P=0.034);其次,将PLA 2R阳性组根据不同PLA 2R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PLA 2R表达相关。 结论:研究中2/3的HBV-MN患者存在肾组织PLA 2R阳性表达,PLA 2R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PLA 2R的表达相关,可能是PLA 2R阳性HBV-MN重要的发病机制。
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abstractsObjective:To investigate the expression of HBV X, gene mutation in M type phospholipase 2 receptor (PLA 2R) in hepatitis B associated membranous nephropathy (HBV-MN) and its possible pathogenesis. Methods:According to the result of PLA 2R immunofluorescence detection in renal tissue, 103 patients with HBV-MN confirmed by renal biopsies were divided into two groups: PLA 2R positive group (n=66) and PLA 2R 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 2R 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 ( X2=7.449, P=0.006) and MN stage II-III ( X2=10.15, P=0.034). Secondly, the correlation analysis of Spearman between PLA 2R 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 PLA2R. Conclusions:The positive expression of PLA 2R in renal tissue was found in 2/3 HBV-MN patients. The PLA 2R 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 2R, which may be an important pathogenesis of PLA 2R positive HBV-MN.
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