SKLB010对MRL/lpr小鼠尿蛋白和单核细胞趋化蛋白-1表达的影响
Effect of SKLB010 on albuminuria and monocytes chemotactic protein-1 expression in MRL/lpr mice
作者:宋丽芳;王飞;胡小红;童擎一;李怡;吴晓华;
Author:
收稿日期: 年卷(期)页码:2011,26(02):-124-126
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:单核细胞趋化蛋白-1;尿蛋白;CD68;SKLB010
Key words:
基金项目:国家“重大新药创制”科技重大专项项目(2009ZX09102-045);;
教育部留学回国人员科研启动基金(JS20081007506765)
中文摘要
目的探讨小分子药物SKLB010对自发性狼疮小鼠肾脏中单核细胞趋化蛋白-1(MCP-1)表达的影响,研究SKLB010对MRL/lpr狼疮小鼠的治疗作用,并初步探讨其作用机制。方法将20只8周龄狼疮小鼠,随机分为SKLB010治疗组与模型组。治疗组经ig口服50 mg·kg-1.d-1 SKLB010后,观察小鼠的尿蛋白、肾功能与肾脏病理的改变。运用免疫组织化学,检测MRL/lpr狼疮小鼠肾组织中MCP-1、CD68的表达。结果模型组狼疮小鼠的尿蛋白水平上调,肾小球基底膜增厚,系膜基质增多,肾组织中MCP-1表达上调,CD68阳性细胞数明显增多。与模型组相比,治疗组狼疮小鼠的尿蛋白水平下降,肾组织中MCP-1表达减少,CD68阳性细胞数减少。结论 SKLB010对MRL/lpr小鼠的自发狼疮肾炎具有治疗作用,其机制可能通过抑制肾组织中MCP-1的表达,减少肾组织单核细胞的浸润,从而延缓狼疮性肾炎的病理损害。
参考文献
[1]Stephen DM,Sue JW,Kjell T,et al.Glomerular expression ofmonocyte chemoattractant protein-1 is predictive of poor renalprognosis in paediatric lupus nephritis[J].Nephrol DialysisTransplant,2008,23(11):3521-3526.
[2]Tesch G,Stefanie M,Andreas S,et al.Monocyte chemoattractantprotein 1-dependent leukocytic infiltrates are responsible for au-toimmune disease in MRL-Faslpr mice[J].J Exp Med,1999,190(12):1813-1824.
[3]Luo Y,Ma L,Zheng H,et al.Discovery of(Z)-5-(4-me-thoxybenzylidene)thiazolidine-2,4-dione,a readily availableand orally active glitazone for the treatment of concanavalin A-induced acute liver injury of BALB/c mice[J].J Med Chem,2010,53(1):273-281.
[4]Nikolic PD,Atkins C.The role of macrophages in glomerulone-phritis[J].Nephrol Dialysis Transplant,2001,16(5):3-7.
[5]Kevin SE,PAUL C.Macrophages and progressive tubulointersti-tial disease[J].Kidney Inter,2005,68:437-455.
[6]Zoja C,Liu XH,Donadelli R,et al.Renal expression of monocytechemoattractant protein-1 in lupus autoimmune mice[J].J AmSoc Nephro,1997,8(5):720-729.
[7]Yamauchi F,Kashem A,Endoh M,et al.Detection of monocytechemoattractant protein-1(MCP-1)and its receptors in me-sangial proliferative glomerulonephritis[J].Nephrology,2007,2(2):93-99.
[8]Tamura M,Aizawa R,Hori M,et al.Progressive renal dysfunctionand macrophage infiltration in interstitial fibrosis in an adenine-induced tubulointerstitial nephritis mouse model[J].HistochemCell Biol,2009,131(4):483-490.
[9]Marcia VP,Julio CSV,Christine M,et al.Rosiglitazone decreasesblood pressure and renal injury in a female mouse model of sys-temic lupus erythematosus[J].Am J Physio-Regul,Integ Com-par Physiol,2009,296:1282-1289.
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