肥大细胞在肥胖相关性肾病肾组织损伤中的作用

Obesity-related glomerulopathy:mast cells infiltration and renal damage

目的:观察肥胖相关性肾病(obesity related glomerulopathy,ORG)患者肾组织肥大细胞数量、分布特点及其与病情的关系,探讨肥大细胞与ORG肾组织损伤及病情进展之间的关系。方法:选取经肾活检确诊的ORG39例,应用免疫组化及双重免疫荧光法检测肾组织中肥大细胞(类胰蛋白酶)和巨噬细胞(CD68)分布情况,分析两者与临床病理之间的关系。结果:ORG患者肾组织中肥大细胞数显著高于对照组(P<0.01),其主要分布在肾间质,以萎缩的肾小管和间质纤维化处更多见,并可见肾小管炎;肾小球内未见肥大细胞浸润,但球囊周围可见肥大细胞浸润;小血管周围也可见肥大细胞浸润。肾间质肥大细胞数与体质量指数(body mass index,BMI)(r=0.364,P<0.05)、收缩压(r=0.459,P<0.01)、舒张压(r=0.347,P<0.05)、尿N-乙酰-β-D-葡萄糖苷酶(NAG)(r=0.324,P<0.05)、血清肌酐(SCr)水平(r=0.637,P<0.01)、肾小球球性硬化(r=0.409,P<0.01)、肾小球节段硬化(r=0.457,P<0.01)、肾小管萎缩(r=0.470,P<0.01)和肾间质纤维化(r=0.669,P<0.01)指标间成正相关,与采用MDRD公式计算的肾小球滤过率(eGFR)水平呈负相关(r=-0.559,P<0.01)。ORG患者肾组织巨噬细胞数也显著高于对照组,且主要分布在有较多炎性细胞浸润的肾间质中,肾小球内也有少量浸润。巨噬细胞数量与间质炎细胞数量呈正相关(r=0.476,P<0.01)。双重免疫荧光染色提示巨噬细胞与肥大细胞在分布上有一定的一致性。多元回归分析显示肾间质肥大细胞浸润程度是影响eGFR水平的独立因素。结论:本研究证实ORG患者肾间质肥大细胞数量增多,并主要分布在肾小管周围、间质纤维化处和肾小球球囊周围,其数量与BMI、血压、肾小管损伤及肾功能进展之间存在显著的相关性,表明肥大细胞参与了ORG的发生和发展过程。

Objective：Obesity related glomerulopathy （ORG） has become an increasing renal disease in China. Inflammatory responses play an important role in the progression of ORG. Mast cells contribute to diet-induced obesity by producing cytokines and protease. To investigate if mast cells are also involved in ORG, we examined mast cell infiltration and its correlation with the progression of renal injury. Methodology：Thirty-nine patients with biopsy-proven ORG and 10 non-obese donors as control were included in this study. Tryptase and CD68 were used for detecting mast cells and macrophages, respectively, by immunohistochemistry in both groups. Results： Mast ceils were detected in fibrotic interstitial and periglomerular areas mostly, but not within glomeruli. Tubulitis was observed. The density of mast cells was significantly increased in ORG compared with the control group, and it was well correlated with body mass index （BMI） （r =0. 364,P 〈0. 05）, systolic blood pressure （r =0. 459,P 〈0. 01 ）, diastolic blood pressure （r =0. 347,P 〈0. 01 ）, N-acetyl-β-D-glucosaminidase （r = 0. 324, P 〈 0. 05 ）, serum creatinine （ r = 0. 637, P 〈 0. 01 ）, tubular atrophy （ r = 0. 47, P 〈 0. 01 ） and interstitial fibrosis （ r = 0. 669, P 〈 0. 01 ）. In contrast, it was negatively correlated with eGFR （ r = - 0. 559, P 〈 0. 01 ）. Macrophages were accumulated focally in the tubular interstitium with other infiltrated cells, and their density was positively correlated with the number of interstitial infiltrated cells （ r = 0. 476, P 〈 0. 01 ）. Multivariate regression showed that the number of mast cells was the critical factor for eGFR level （ R2 = 0. 44, P 〈 0. 05 ）.Conclusion： The patients with ORG had an increase in the number of interstitial mast cells, which was correlated positively with BMI, blood pressure, serum creatinine, and tubular injury, but negatively with eGFR. These data suggested a role for mast cells in tubular atrophy and interstitial fibrosis. Further functional studies are required to determine the role of mast cells in tubular injury of ORG.