活动性肾小球肾炎中过氧化脂质体增殖激活受体γ在肾脏的表达

目的 :研究过氧化脂质体增殖激活受体γ(PPAR γ)在人肾小球肾炎病变活动时肾组织中的表达变化。方法 :根据临床及肾活检病理诊断 ,选择炎症病变明显活动的病人 ,细胞性新月体肾小球肾炎 (RPGN) 17例、狼疮性肾炎 (Ⅳ型 ) (LN) 15例 ,并以炎症病变轻微的轻度系膜增生性IgA肾病 (IgAN) 7例和无炎症病变肾小球微小病变 (MCD) 10例为对照。分别收集各组病人临床资料 ,光镜下观察并计数肾脏病变活动指数 ;免疫组化和原位杂交方法观察肾组织PPAR γ蛋白和mRNA表达。结果 :LN和RPGN组病人临床上呈明显病变活动表现 ,肾脏病理活动指数显著高于IgAN和MCD组。肾组织PPAR γ免疫组化显示PPAR γ在MCD组未见表达 ;在IgAN组肾小球和肾小管少量表达 ;在病变活动的RPGN和LN组肾小球和肾小管表达显著上调。相关分析结果显示 ,在病变活动性指数与肾小球和肾小管PPAR γ染色阳性细胞数间呈显著相关性 (相关系数分别为 0 .4 78,P <0 .0 1;0 .5 13,P<0 .0 1)。原位杂交方法也进一步证实LN和RPGN组肾小管上皮细胞PPAR γmRNA表达较IgAN和MCD组显著上调。结论 :活动性肾小球肾炎病人的肾组织PPAR γ表达上调 ,这可能是肾组织对炎症应激反应的一种表现 ,并预示PPAR γ可能在肾小球炎症过程中发挥重要作用

PPAR-γ expression in the kidney of actively proliferating glomerulonephritis

OBJECTIVE: To investigate peroxisome proliferator-activated receptor gamma (PPAR-gamma) expressions in patients with actively proliferating glomerulonephritis such as type IV lupus nephritis (LN) and cellular crescentic glomerulonephritis (RPGN). METHODS: All patients were divided into 4 groups as follows: RPGN (17 cases); LN type IV (15 cases); mild mesangial proliferative IgA nephropathy (IgAN, 7 cases) and minimal change disease (MCD, 10 cases). Clinical parameters, immunohisto-chemistry stain and in situ hybridization of renal biopsy specimens were performed. RESULTS: Clinically, proteinuria and hematouria were increased and Ccr were decreased in LN and RPGN patients, and increased ESR and decreased complement C3 were found in group LN. Active index of renal specimens were significantly higher in LN and RPGN groups than in IgAN and MCD groups. Renal specimens of MCD patients showed no positive PPAR-gamma staining in all sections; little immunoreactivity was detected in sections of glomerular, tubular and interstitial cells from IgAN patients. Glomerular positive staining of PPAR-gamma in renal sections in LN and RPGN patients[(3.3 +/- 1.8) and (2.8 +/- 1.2) cells per section of glomerulus, respectively] were significantly increased compared with that in IgAN patients [(0.7 +/- 0.5) cells per section of glomerulus]. Similarly, tubular positive staining of PPAR-gamma in LN and RPGN patients (27.38 +/- 12.46, 23.36 +/- 10.55) were also elevated compared with that in IgAN and MCD patients(6.51 +/- 3.49, 1.72 +/- 0.31). The relevance assay results showed positive relationship between active index and glomerular or tubular PPAR-gamma immunohisto-chemistry staining cell numbers (0.478, P < 0.01; 0.513, P < 0.01). Tubular PPAR-gamma mRNA expression in LN and RPGN patients was upregulated by in situ hybridization. CONCLUSION: Our results demonstrate in vivo that PPAR-gamma expression was increased in active glomerulonephritis patients accompanied with clinical and pathological active inflammation. These data suggest that increase of PPAR-gamma expression in renal cells may play an important role in response to inflammatory stress.