骨调素和巨噬细胞集落刺激因子在糖尿病大鼠肾组织中的表达及霉酚酸酯的干预作用  

Expression of OPN and macrophage colony stimulating factor in diabetic rats and intervention of mycophenolate mofetil

作　　者：张燕[1] 王威[1] 陈兵[2] 关广聚[2] 李学刚[2] 

机构地区：[1]山东烟台毓璜顶医院肾内科,山东烟台264000 [2]山东大学第二医院肾内科,山东济南250033

出　　处：《中国病理生理杂志》2008年第6期1173-1177,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No30570866)

摘　　要：目的:研究骨调素(OPN)和巨噬细胞集落刺激因子(M-CSF)在糖尿病大鼠肾组织中的表达及免疫抑制剂霉酚酸酯(MMF)的干预作用,旨在探讨MMF对糖尿病肾病(DN)的保护作用及机制。方法:Wistar大鼠行右肾切除术2周后,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)。腹腔注射链脲佐菌素(STZ,65mg/kg)诱发糖尿病模型,MMF15mg.kg-1.d-1灌胃。检测各组8周末的左肾重/体重比值、24h尿蛋白(Upro)、血糖(BG)、血肌酐(Scr),观察肾脏形态学变化,免疫组化检测肾组织中OPN、M-CSF及CD68表达,荧光实时定量PCR测定肾组织中OPNmRNA表达。结果:与对照组相比,DM组大鼠血糖、Upro、肾重/体重比值均显著上升(P<0.01);肾间质纤维化面积扩大(P<0.01);肾组织内OPN、M-CSF、CD68表达及OPNmRNA的表达均显著上调(P<0.01)。MMF干预后,上述指标除血糖外均被明显抑制(P<0.05或P<0.01)。结论:MMF减少糖尿病大鼠肾组织中OPN、M-CSF、CD68及OPNmRNA的表达,降低蛋白尿,预防肾损伤。MMF明显抑制DN肾小管-间质损害,可能与其抑制巨噬细胞的趋化与增殖有关。AIM ： To explore the effect of mycophenolate mofetil （MMF） on expression of osteopotin （OPN） and macrophage colony stimulating factor （M -CSF） in diabetic rats with renal tubulo -interstitial injury. METHODS： Diabetes was induced in uninephrectomized male Wistar rats by peritoneal injection of streptozotocin （65 mg/kg）. The rats were randomly divided into three groups ： control group （ NC）, diabetic group （DM） and MMF treated group [ DM ＋ MMF, treatment of MMF （15 mg·kg^-1 · d^-1） by gavage from the next day of the induction for 8 weeks]. Serum biochemistry, 24 h urinary protein and the ratio of left kidney weight/body weight were determined after 8 weeks. The renal tubulo - interstitial morphological change was observed, immunohistochemical method was used to analyze the expression of OPN, M - CSF and CD68. The mRNA of OPN in renal tissue was amplified by quantitative real - time PCR. RESULTS： Compared with control group, serum glucose level, 24 h urinary protein and the ratio of left kidney weight/body weight were significandy increased （ P 〈 0.01 ）, and the relative area of interstitial fibrosis was also significantly enlarged in DM group （ P 〈 0.01 ）. Compared with NC group, the expressions of OPN, M-CSF, CD68 protein and OPN mRNA were significandy up- regulated in DM group （P 〈 0.01 ）. After intervention with MMF, the upregulations of the above -mentioned parameters, except blood glucose and serum creatinine, were all significantly inhibited （P 〈0.05 or P 〈0.01 ）. CONCLUSION： The expressions of OPN, M-CSF and CD68 in renal tubulointerstitial decrease in diabetic rats treated with MMF. MMF also inhibits the level of OPN mRNA, reduces proteinuria and prevents renal injury. MMF plays an apparently protective role in renal tubulointerstitial iniurv , probablv associated with inhibiting chemokine and proliferation on macronhages.

关 键 词：糖尿病 大鼠 霉酚酸酯 骨桥蛋白 巨噬细胞集落刺激因子 

分 类 号：R587.1[医药卫生—内分泌]