狼疮性肾炎患者肾脏伴侣蛋白、肾素-血管紧张素系统的变化及意义

目的测定狼疮性肾炎(LN)患者的热休克蛋白70(HSP70)、泛素、血管紧张素Ⅱ 1型受体(AT1R)、血管紧张素Ⅱ 2型受体(AT2R)、血管紧张素转换酶(ACE)等,探讨LN患者肾素-血管紧张素系统(RAS)是否被激活及其与伴侣蛋白可能存在的关系.方法 27例LN患者(LN组)根据系统性红斑狼疮(SLE)活动指数(SLE-DAI)进一步分为活动亚组(13例,SLE-DAI≥15)和非活动亚组(14例,SLE-DAI<15);对照组为9例隐匿性肾炎患者(肾组织活检结果为轻微病变).对所有肾穿刺标本行HSP70、泛素、AT1R、AT2R、ACE测定.采用TUNEL法测定肾内凋亡细胞的表达.对SLE活动度、病理变化、RAS活性与伴侣蛋白的表达进行相关分析.结果 LN组的 HSP70表达显著低于对照组,而泛素、AT1R、AT2R、ACE和凋亡细胞的表达明显升高(P值均<0.05).活动亚组与非活动亚组的HSP70及泛素表达的差异无显著性(P>0.05),活动亚组的ACE、AT2R和凋亡细胞的表达显著高于非活动亚组,而AT1R表达显著降低(P值均<0.05).小管间质中,HSP70表达与病理慢性指数相关(r＝0.432,P＝0.028);肾小球与肾小管中,泛素表达与AT1R或AT2R均相关(r值分别＝0.574、0.616.P值均<0.05).结论伴侣蛋白和RAS可能参与了LN病理变化的发病机制.

Relationship between chaperones and renin-angiotensin system in biopsied renal tissue from lupus nephritis patients

Objective Abnormalities of molecular chaperones have been regarded as one of the mechanisms involved in the pathogenesis of both systemic lupus erythematosus (SLE) and glomerulonephritis. Blockage of renin-angiotensin system (RAS) has been used in the clinical treatment for lupus nephritis (LN). However, the relationship between RAS and molecular chaperones remains unclarified. Therefore, this study was conducted to investigate whether the activation of renal RAS was correlated with molecular chaperones. Methods Renal biopsy tissue were collected from 27 SLE patients for morphometric analyses, expressions of angiotensin converting enzyme (ACE), angiotensin type 1 and 2 receptors (AT1R and AT2R), HSP70 and ubiquitin in both glomeruli and tubules detected by immunohistochemistry. Correlative analyses were performed to examine the relationship between disease activity, pathological changes, RAS activity and expression of molecular chaperones. The apoptotic cells in the kidney were detected by TUNEL method. Another 9 cases diagnosed as minor glomerular lesion served as control. According to SLE-DAI, 13/27 cases were classified as ACTIVE, while the other 14/27 as INACTIVE. Results In LN patients, expressions of ubiquitin, AT1R, AT2R, ACE and the number of apoptotic cells were significantly increased compared with those of the control, while the HSP70 expression in LN patients was significantly lower (P<0.05, respectively). The HSP70 expression in the tubulointerstitium was correlated with the chronic histological index (r=0.432, P=0.028). In both glomerular and tubulointerstitial regions, ubiquitin expression was positively correlated with either AT1R or AT2R (P<0.05, respectively) despite that the expression of AT1R was significantly lower in ACTIVE group than that in INACTIVE group. Conclusion Chaperone and RAS abnormalities are involved in the pathogenesis of LN with interrelationship of each other.