TLR活化参与环孢素A诱发的慢性肾小管间质损伤  

Activated Toll-like receptors participate in chronic renal tubulointerstitial injury induced by cyclosporine A

作　　者：洪英礼[1] 金英顺[1] 崔镇花[1] 陈瑛[1] 李灿[1] 

机构地区：[1]延边大学附属医院肾内科,吉林延吉133000

出　　处：《中国病理生理杂志》2011年第3期555-559,共5页Chinese Journal of Pathophysiology

摘　　要：目的:探讨慢性肾小管间质损伤的免疫发生机制。方法:Sprague-Dawley大鼠皮下注射环孢素A(CsA,15 mg·kg-1·d-1)4周建立慢性肾小管间质损伤模型,对照组给予皮下注射橄榄油(1 mL·kg-1·d-1)。检测两组大鼠的肾功能;三色染色和免疫组织化学染色确定肾小管间质损伤程度(炎性细胞浸润和带状纤维化);荧光原位杂交技术和免疫组织化学染色分别观察肾内Toll样受体(TLR)、TLR配基-热休克蛋白70(HSP70)及补体系统成分(C3、C4d和C9)的表达。结果:与对照组相比,肾毒性组表现为肾功能低下、肾间质大量ED-1阳性细胞浸润、肾小管间质带状纤维化(P<0.01)。同时,肾毒性组TLR2和TLR4的mRNA和蛋白水平明显上调;TLR配体HSP70免疫活性增加;补体C3、C4d和C9的免疫活性显著增加。这些高表达的免疫成份主要位于肾小管间质受损部位。结论:激活的肾内天然免疫与CsA引起的慢性肾小管间质损伤有关。AIM： To study the role of innate immunity in the pathogenesis of renal tubulointerstitial injury.METHODS： The model of nephrotoxic nephropathy was induced by chronic cyclosporine A（CsA） administration（15 mg·kg-1·d-1 for 4 weeks） in Sprague-Dawley rats.The tubulointerstitial injury,characterized by inflammatory cell infiltration and striped fibrosis,was examined by the methods of immunohistochemistry and trichrome staining.The expression of Toll-like receptors（TLR）,TLR ligand heat-shock protein 70（HSP70）and intrarenal complement elements（C3,C4d and C9） was evaluated in rat kidneys by the methods of in situ hybridization and immunohistochemistry.RESULTS： Compared with the normal rats,the rats exposed to CsA showed impaired renal function,ED-1-positive cell infiltration and striped tubulointerstitial fibrosis（all P〈0.01）.Concomitantly,CsA treatment up-regulated the expression of TLR2 and TLR4 at mRNA and protein levels in renal tubular cells,accompanied by increased putative TLR ligand（HSP70） and the immunoreactivity of intrarenal complements.These up-regulated innate immunity components were located in the areas of severe tubulinterstitial injury.CONCLUSION： CsA-induced renal tubulointerstitial injury is closely associated with the activation of intrarenal innate immunity.

关 键 词：肾小管间质损伤 天然免疫 受体 Toll样 热休克蛋白质70 补体 环孢菌素 

分 类 号：R363[医药卫生—病理学]