老龄大鼠2型糖尿病肾病对肾1-α羟化酶及骨质密度影响的实验研究

Effect of diabetic neuropathy on renal 1-α hydroxylase and bone mineral density in old type 2 diabetic rats

目的观察老龄大鼠2型糖尿病肾病对肾1-α羟化酶及骨密度(BMD)的影响。方法18月龄Wistar大鼠40只,分为正常对照组、糖尿病组、处理1组和处理2组,用放免法测定各组大鼠24h尿白蛋白、血25-(OH)D3和1,25-(OH)2D3水平,双能X线骨密度测量仪(DEXA)测定各组大鼠腰椎、股骨BMD。结果与正常组比较,其他3组24h尿白蛋白显著升高,而BMD显著降低(P<0·05),处理2组BMD高于处理1组和糖尿病组(P<0·05)。处理1组25-(OH)D3有升高趋势,无统计学意义(P>0·05)。处理2组1,25-(OH)2D3与正常对照组相当,高于糖尿病组和处理1组,差异有统计学意义(P<0·05)。糖尿病组大鼠1,25-(OH)2D3与尿白蛋白呈负相关(r=-0·7705,P=0·009),与骨密度呈正相关(股骨r=0·8707,P=0·001,腰椎r=0·8827,P=0·007)。结论老龄大鼠2型糖尿病肾病致肾1-α羟化酶活性下降,肾1-α羟化酶活性下降与BMD降低关系密切。

Objective To investigate the change of renal 1-alpha hydroxylase and its effect on bone mineral density in the old rats with type 2 diabetic nephropathy. Methods Forty Wistar rats of 18 months old were randomly divided into normal control （N）, diabetes （D）, diabetes treated with vitamin D3 （T1） and diabetes treated with 1 -α （OH） D3 （ T2 ） groups, respectively. Ten rats in each group. Dual energy X-ray absorption （DEXA） was used to determine bone mineral density （BMD） of lumbar spines and femoral bone. 24 h urinary protein excretion, serum 25 （OH） D3 and 1,25 （OH） 2D3 were measured by radioimmunoassay. Results Compared with controls, 24 h urinary protein excretion increased remarkably D, T1 , T2 groups, while BMD greatly decreased, much lower in D group and T1 group than T2 group （ P 〈 0. 05 ）. The level of serum 25 （OH） D3 had no marked changes in N, D and T2 groups, while T1 group seemed higher （P 〉0. 05）. The level of 1,25 （OH）2D3in N group was the same to T2 group, but higher than D, T1 groups （P〈0. 05）. In the old type 2 diabetic rats, 1-α （OH） D3 showed a negative correlation with 24 h urinary protein excretion （ r = - 0. 770 5, P=0.009） and positive correlation with BMD （femoral bone： r=0.8707, P = 0.001; lumbar spine： r =0. 882 7, P = 0. 007 ）. Conclusion Type 2 diabetes mellitus results in the decline of activity of renal 1-alpha hydroxylese and the decline of BMD. 1-α（OH）D3 would effectively reverse the change of BMD.