PDGF及PDGFR在大鼠肾间质纤维化过程中的作用  

Role of PDGF and PDGFR in murine renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO)

作　　者：徐惠[1] 官阳[1] 杨木兰[1] 周泽斌[1] 张春明[1] 

机构地区：[1]华中科技大学同济医学院病理学系超微病理研究室,湖北武汉430030

出　　处：《中国现代医学杂志》2007年第19期2354-2358,共5页China Journal of Modern Medicine

摘　　要：目的探讨PDGF及其受体PDGFR在单侧输尿管梗阻大鼠肾间质纤维化中的作用。方法24只SD大鼠,采用单侧输尿管梗阻模型,分别于造模后第3、7、14及21天各处死6只大鼠,取双侧肾脏(未手术侧为对照组)分别做光镜和电镜检查,观察其病理改变。并以免疫组织化学法检测肾组织中PDGF-A、PDGF-B、PDGFR-α、PDGFR-β以及α-SMA(活化肌成纤维细胞的标志)和Ⅲ型胶原的表达。结果与对照组相比PDGF-A、PDGF-B、PDGFR-α、PDGFR-β在不同时间点的梗阻肾脏中表达均增强,主要定位于扩张或萎缩的皮质肾小管上皮细胞,肾间质有少量表达。随着梗阻时间的延长,肾间质表达α-SMA的细胞和Ⅲ型胶原逐渐增多,两者呈正相关关系,与对照组相比差异有显著性(P<0.05)。肾间质α-SMA、Ⅲ型胶原的表达与肾小管PDGF-B和PDGFR-β的表达呈正相关,而与PDGF-A和PDGFR-α的表达无明显相关性。结论大鼠单侧输尿管梗阻(UUO)模型中受损的肾小管过度表达PDGF-B、PDGFR-β,可促进肌成纤维细胞的形成和Ⅲ型胶原的沉积,在肾间质纤维化过程中可能起重要作用。[Objective] To study the role of PDGF and PDGFR in murine renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction （UUO）. [Methods] left ureteral ligation resulting in UUO was performed in 24 male SD rats. Animals were killed at days 3, 7, 14 and 21, respectively, after the operation （n =6 at each time point）, and renal samples were obtained, the right kidneys were used as controls. Routine light and electron microscopic examination were applied to observe the pathologic changes of kidneys. Serial sections were immunohistochemically investigated for PDGF ligands （PDGF-A, -B） and PDGF receptors （PDGFR-α,-β）, as well as α-SMA （a marker for myofibroblast） and type Ⅲ. collagen. [Results] In comparison with the unobstructed kidneys, increased immunosraining for PDGF-A, -B and PDGFR-α,-β Was observed at all time points in obstructed kidneys and located mainly in atrophic or dilated proximal and distal tubules. PDGF and PDGFR were also expressed in interstitial cells in the areas containing inflammatory infiltration. The number of α-SMA-positive cells and deposition of type Ⅲ collagen in tubulointerstitium were increased progressively as time went by （P 〈0.05）. The overexpression of PDGF-B and PDGFR-β in injury tubules was related to the accumulation of type Ⅲ collagen and the number of α-SMA-positive cells in tubulointerestitium （P 〈0.05）. A significant correlation was also found on the optical density of positive reaction between α-SMA and type Ⅲ collagen in tubular interstitium （P 〈0.05）. [Conclusions] In UUO model, the overexpression of PDGF-B and PDGFR-β in injury tubules could promote the activation of myofibroblast and the accumulation of type Ⅲ collagen. In a word, PDGF-B/PDGFR-β might play an important role in the pathogenesis of tubulointerstitial fibrosis in UUO model.

关 键 词：肾间质纤维化 PDGF PDGFR 

分 类 号：R692[医药卫生—泌尿科学] R-332[医药卫生—外科学]