肥大细胞与慢性马兜铃酸肾病间质纤维化关系的初步探讨

Preliminary Studies on Relationship Between Mast Cells and Renal Interstitial Fibrosis with Chronic Aristolochic Aacid Nephropathy

目的:初步探讨慢性马兜铃酸肾病(CAAN)患者肾间质肥大细胞浸润与间质纤维化之间关系。方法:随机选取CAAN16例、非CAAN的慢性间质性肾炎(CIN)16例及微小病变病(MCD)11例患者肾穿刺组织作为研究对象。采用免疫组织化学、免疫荧光双重染色方法观察类胰蛋白酶(Try)染色阳性的肥大细胞(MCs)、蛋白酶活化受体-2(PAR-2)、转化生长因子-β1(TGF-β1)及Ⅰ型胶原(ColⅠ)表达的变化。结果:与MCD对照组相比,CAAN、CIN组肾间质MCs数量、肾小管上皮细胞PAR-2和TGF-β1及肾间质ColⅠ表达面积显著增加,而CAAN与CIN两组间上述指标无统计学差异;MCs数量与肾小管上皮细胞PAR-2和TGF-β1表达面积及肾间质ColⅠ表达面积呈显著正相关,肾小管上皮细胞PAR-2与TGF-β1表达面积之间也呈显著正相关;MCs数量分别与肾间质PAR-2和TGF-β1阳性细胞数量呈显著正相关,PAR-2阳性细胞数量和TGF-β1阳性细胞数量间也呈显著正相关。肾间质中Try染色阳性细胞与PAR-2或TGF-β1染色阳性细胞存在部分重叠。结论:MCs可能参与CAAN细胞外基质蓄积,推理可能与活化PAR-2,增加TGF-β1表达相关。

Objective： To explore the potential relationship between tryptase- positive mast cells （MCs） infiltration into the renal interstitium and renal interstitial fibrosis in patients with chronic aristolochic acid nephropathy （CAAN）. Methods：Renal biopsy specimens from CAAN （ n = 16）, chronic interstitial nephritis （CIN） （ n = 16） and minimal change diseases （MCD） （ n = 11 ） were studied. Immunohistochemistry staining assay and immunofluorescence double - staining assay were used to detect the amount of MCs, the expression of proteinase activated receptor- 2 （PAR - 2）, transforming growthfactor β1 （TGF -β1 ） and collagen type Ⅰ （Col Ⅰ ） in the renal tissues. Results： The amount of MCs, the relative immunostaining positive areas of PAR-2 and TGF-β1 in renal tubular epithelial cells （RTECs） ,as well as the relatively immunostainingpositive area of Col Ⅰ in the renal interstitium were significantly higher in CAAN and CIN groups than those in MCD group （P 〈 0.0 1 ）. There were no statistical differences between CAAN and CIN group about the above- mentioned parameters.There were significantly positive correlations between amount of MC,s and the relatively immunostaining- positive area of PAR - 2, TGF - β1 in RTEC,s as well as that of Col I in the renal interstitum（ r = 0. 503,0. 489,0.521, P 〈 0.01 ）, respectively,meantime significantly positive relationship between the relatively immunostaining-positive area of PAR- 2 and that of TGF-β1 was also observed （ r = 0. 724, P 〈 0.01 ）. There were significantly positive correlations between amount of MCs and that of PAR - 2 - positive cells or TGF- β1 positive cells in the renal interstitum. （ r =0. 670,0. 673,P〈0.01）, respectively, and there was significantly pssitive correlation between amount of PAR- 2 - positive cells and that of TGF- β1 - positive（ r = 0. 767, P 〈0.01）. Immunofluorescence double- staining assay showed that sane tryptase- positive cells overlapped with PAR- 2 - positived cells or TGF- β1 - posifived cells in the renal interstitium. Conclusion： MCs in the renal interstitium are suggested to be involved into the accumulation of extracellular matrix with CAAN and CIN. The mechanism is supposed to have close relationship with enhancement of the expression of TGF- β1 after activation of PAR- 2 by tryptase.