Wu Kaiyin, Zhou Tong, Sun Guizhi, Wang Weiming, Zhang Yumei, Zhang Yanyun, Hao Li, Chen Nan
Department of Nephrology, Rui Jin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
Cell Mol Immunol. 2006 Jun;3(3):213-20.
To observe the accumulation of dendritic cells (DCs) in rat remnant kidney and its contribution to tubulointerstitial fibrosis, under influence of valsartan on DCs, a rat remnant kidney model was established by subtotal nephrectomy. Four experimental groups were included: normal, sham, model (SNx) and the group treated with Valsartan (SNxV). Rats were killed at week 1, 4 and 12, respectively. CD1a+CD80+ DCs were assayed by double immunostaining method and the images were analyzed with Axioplan 2 microscopy. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin was analyzed by immunohistochemistry or semi-quantitative RT-PCR, and the level of tubulointerstitial firosis (TIF) was scored. CD1a+CD80+ DCs were gradually increased among renal tubules, interstitium and vessels, especially in interstitium, and the number of DCs in model group at week 12 was much more than that in model groups at week 1 or 4. The expressions of P-selectin, TGF-beta1, alpha-SMA, collagen III and fibronectin in tubulointerstitial areas and the degree of TIF was increased substantially in model group at week 12. The accumulation of DCs in interstitium was well associated with the loss of renal function and the progression of tubulointerstitial fibrosis. Valsartan treatment inhibited the local accumulation of DCs and attenuated renal tubulointerstitial damage. The local DCs accumulation was related to tubulointerstitial fibrosis and renal dysfunction following renal ablation. Blockade to angiotensin II might be a potent way to attenuate renal immuno-inflammatory injury.
为观察大鼠残余肾中树突状细胞（DCs）的聚集情况及其对肾小管间质纤维化的作用，以及缬沙坦对DCs的影响，通过次全肾切除术建立大鼠残余肾模型。实验分为四组：正常组、假手术组、模型组（SNx）和缬沙坦治疗组（SNxV）。分别于第1、4和12周处死大鼠。采用双重免疫染色法检测CD1a+CD80+ DCs，并通过Axioplan 2显微镜分析图像。采用免疫组织化学或半定量RT-PCR分析P-选择素、转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）、Ⅲ型胶原和纤连蛋白的表达，并对肾小管间质纤维化（TIF）程度进行评分。CD1a+CD80+ DCs在肾小管、间质和血管中逐渐增多，尤其是间质中，模型组第12周时DCs数量远多于第1周或第4周时的模型组。模型组第12周时肾小管间质区域P-选择素、TGF-β1、α-SMA、Ⅲ型胶原和纤连蛋白的表达及TIF程度显著增加。间质中DCs的聚集与肾功能丧失及肾小管间质纤维化进展密切相关。缬沙坦治疗可抑制DCs的局部聚集并减轻肾小管间质损伤。局部DCs聚集与肾切除术后肾小管间质纤维化及肾功能障碍有关。阻断血管紧张素II可能是减轻肾脏免疫炎症损伤的有效方法。
