赵安菊,黄颂敏,欧三桃,王里,陈超
ZHAO Anju1,HUANG Songmin2,OU Santao2,WANG Li1,CHEN Chao1 (1.Department of Cadre's ward

• 1:贵州省人民医院干医科
• 2:四川大学华西医院肾内科

摘要(Abstract)：

目的:检测糖尿病肾病(DN)大鼠肾脏中骨形成蛋白2(BMP-2)和基质Gla蛋白(MGP)的基因表达量的变化规律,探讨其对糖尿病肾病的影响。方法:设对照组(N组)及糖尿病肾病组(DN组,STZ诱导的DN大鼠模型);采用实时荧光定量PCR(Real-Time PCR)方法检测4、12、24周DN大鼠及正常大鼠肾脏中BMP-2及MGP的基因定量,茜素红染色观察肾实质内小动脉周围钙盐沉积。结果:(1)DN组各时间点血糖及24 h尿蛋白量均较N组显著增高(P<0.05),自第12周开始,DN组血肌酐、血磷较N组明显增高(P<0.05);(2)DN组4周时BMP-2 mRNA已有表达,随时间延长表达逐渐升高,24周最高(P<0.05);DN组MGP表达量4周最高,随时间延长逐渐降低,24周最低(P<0.05),而N组BMP-2和MGP mRNA各时间点表达量差异均无统计学意义;(3)茜素红染色DN组第4～12周时偶见肾内小动脉少许点状红色钙盐沉积,第24周时可见肾实质内小动脉及周围组织有较多红色点片状沉积,N组茜素红染色为阴性;(4)DN组BMP-2和MGP呈显著负相关(r=-0.494,P<0.01),BMP-2表达与尿蛋白、血肌酐、血磷(r=0.422,P<0.01;r=0.743,P<0.01 r=0.671,P<0.01)呈显著正相关,MGP表达与尿蛋白、血肌酐、血磷(r=-0.511,P<0.01;r=-0.490,P<0.01;r=-0.420,P<0.05)呈显著负相关。结论:DN大鼠肾内小动脉钙化前已有血管钙化标志物BMP-2和MGP的表达,随时间延长BMP-2基因表达量逐渐增多,MGP基因表达量逐渐减少,提示DN大鼠肾脏内BMP-2及MGP基因表达量的变化可能参与DN进展。
Objective: To observe the expressions of bone morphogenetic protein-2(BMP-2) and matrix Gla protein(MGP)genes in kidney of diabetic nephropathy rats,and so as to explore their effects to diabetic nephropathy.Methods: Adult Sprague-Dawley male rats were divided into diabetic nephropathy group(group DN) and normal group(group N).DN model was established by STZ induction.The expressions of BMP-2 and matrix Gla protein MGP gene were detected with Real-Time PCR in 4,12 and 24 weeks.Calcium depositing around the renal arteriole was observed by alizarin red staining.Results:(1) Contents of blood glucose and urine protein of group DN at all time points were much higher than those of group N(P<0.05).Serum creatinine and serum phosphorus of group DN were higher than those of group N since the 12th week(P<0.05).(2) BMP-2 mRNA was detectable in group DN in 4 weeks,and gradually increased with the time passing,reached peak at the 12th week.The expression level of MGP mRNA of group DN was evidently increased in 4 weeks,slightly decreased in 12 weeks,reached bottom at the 12th week;No significant difference was found among the expressions at different time points in group N;(3) A little calcium salt was found deposited in the renal arteriole of DN rats in 4 weeks,and a large amount of calcium salt was found in 24 weeks.No calcium was found in control rats.(4)BMP-2 gene expression was negatively correlated with MGP gene expression in DN group(r=-0.494,P<0.01).BMP-2 gene expression was positively correlated with serum creatinine,serum phosphorus and urine protein(r=0.422,P<0.01;r=0.743,P<0.01;r=0.671,P<0.01).MGP gene expression was negatively correlated with serum creatinine,serum phosphorus and urine protein(r=-0.511,P<0.01;r=-0.490,P<0.01;r =-0.420,P<0.05).Conclusions:(1) BMP-2 and MGP mRNA occur in renal arteriole before the formation of vascular calcification.The expression of BMP-2 mRNA gradually increases,and MGP mRNA gradually decreases with time passing;(2) BMP-2 and MGP may play a role in the development of diabetic nephropathy.

关键词(KeyWords)： 糖尿病肾病;骨形态发生蛋白质类;基质Gla蛋白;聚合酶链反应;大鼠,Sprague-Dawley
diabetic nephropathies;bone morphogenetic proteins;matrix Gla protein;polymerase chein reaction;rats,Sprague-Dawley

Abstract:

Keywords:

基金项目(Foundation): 贵州省科技厅基金资助项目(黔科合J字[2008]2299号);; 贵州省卫生厅优秀医学青年科技人才基金项目(gzwkj2010-02-006)

作者(Author): 赵安菊,黄颂敏,欧三桃,王里,陈超
ZHAO Anju1,HUANG Songmin2,OU Santao2,WANG Li1,CHEN Chao1 (1.Department of Cadre's ward

DOI: 10.19367/j.cnki.1000-2707.2011.05.007

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