摘要
目的观察免疫抑制剂霉酚酸酯(MMF)对糖尿病大鼠肾小管-间质单核细胞趋化蛋白-1(MCP-1)及CD68表达的影响,探讨MMF对糖尿病大鼠肾小管间质损伤的保护作用及机制。方法Wistar大鼠行右肾切除术2wk后,随机分为右肾切除对照组(NC)、糖尿病组(DM),霉酚酸酯治疗组(DM+MMF,MMF15mg·kg-1.d-1灌胃)。腹腔注射链脲佐菌素(STZ,65mg·kg-1)诱发糖尿病模型。检测各组8wk末的左肾重/体重比值、24h尿蛋白(Upro)、血糖(BG)、血肌酐(Scr),观察肾小管-间质形态学变化,免疫组化检测肾组织中MCP-1及CD68表达,RT-PCR测定肾组织中MCP-1 mRNA表达。结果与NC组相比,DM组大鼠血糖、Upro及左肾重/体重比值均上升(P<0.01);肾间质纤维化面积扩大(P<0.01);肾组织内MCP-1蛋白、CD68表达及MCP-1 mRNA的表达均上调(P<0.01)。DM+MMF组上述指标除BG和Scr外均被抑制(P<0.05或P<0.01)。结论MMF对糖尿病大鼠肾小管-间质损害具有明显的保护作用,可能与抑制MCP-1基因及蛋白表达有关。
Aim To observe the effect of mycophenolate mofetil（MMF） on expressions of MCP-1 and CD68 in renal tubulointerstitial injury of diabetic rats and explore the mechanism of MMF＇s protective role. Methods Diabetes was induced in uninephrectomized male Wistar rats by peritoneal injection of STZ （65 mg·kg^-1）. Rats were randomly divided into three groups： control group （ NC ）, diabetic group （DM） and treated group （DM ＋ MMF） with MMF（ 15 mg·kg^-1·d^-1）. This study lasted for 8 weeks. 24 h urinary protein, blood glucose and the ratio of left kidney weight/body weight were determined after 8 weeks. The renal tubulointerstitial morphological change was observed, immunohistochemical method was used to analyze expressions of MCP-1 protein and CD68. Expression of MCP- 1 mRNA in renal tissue was measured by quantitative Real-time PCR. Results Compared with NC group, serum glucose level,24 hour urinary protein and the ratio of left kidney weight/body weight were significantly increased（ P 〈 0. 01 ）, and the relative area of interstitial fibrosis was also significantly enlarged in DM group （P 〈0. 01 ） ;Expressions of MCP-1 protein,CD 68 and MCP-1 mRNA were significantly upregulated in DM group （ P 〈 0. 01 ）, but parameters mentioned above, except serum glucose and serum creatinine, were all significantly inhibited in MMF group（ P 〈0. 05 or 0. 01 ）. Conclusions MMF plays an apparent protection on renal tubulointerstitial injury,which is probably associated with down-regulation of MCP-1 expression.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第6期777-781,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30570866)
山东省自然科研基金资助项目(No2005zrb02001)
作者简介
张燕（1968-）女，博士生，副主任医师，研究方向：糖尿病肾病，Fax：0531-8962544；E-mml：zhangyan@medmail．com．cn；
关广聚（1952-），男，博士生导师，主任医师，研究方向：糖尿病肾病发病机制，通讯作者，E-mail：guangj@sdu．edu．cn
