同型半胱氨酸对Kkay小鼠糖尿病肾病作用机制的探讨  

The mechanism of homocysteine in Kkay mice diabetic nephropathy model

作　　者：陆菊明[1] 郭清华[1] 潘长玉[1] 母义明[1] 邹效漫[1] 尹岭[2] 盛春燕[2] 

机构地区：[1]解放军总医院内分泌科,北京100853 [2]解放军总医院神经信息中心,北京100853

出　　处：《中华内科杂志》2004年第8期604-607,共4页Chinese Journal of Internal Medicine

摘　　要：目的 探讨基质金属蛋白酶-9(MMP-9)在同型半胱氨酸(Hcy)加重糖尿病肾病(DN)过程中的可能作用。方法 22～24周龄Kkay糖尿病鼠16只随机分两组:糖尿病组(KA)和高蛋氨酸组(KB),每组8只;C57BL/6小鼠9只为对照组(C57),以相应饲料喂养4个月后取材。测定血糖和血Hcy水平,以PAS染色观察各组肾组织肾小球病理改变,比较肾小球硬化指数(GI)。对肾脏MMP-9表达进行免疫组化染色和半定量图像分析,并以逆转录PCR检测。肾脏MMP-9 mRNA的表达水平。结果 与C57对照组相比,Kkay两组均有不同程度糖尿病肾病病变,其中KB组病变更重,其GI值(283.33)高于KA组(240.00),P<0.05。免疫组化显示KB组肾小球MMP-9阳性着色面积(15.90％)高于KA组(11.14％),P<0.05,MMP-9 mRNA表达水平KB组高于KA组。结论 高Hcy血症具有加重Kkay小鼠糖尿病肾病程度的作用,此作用可能与上调MMP-9的表达水平有关。Objective To study the expression of matrix metalloproteinase-9 (MMP-9) in diabetic nephropathy of Kkay mice with hyperhomocysteinemia. Methods Sixteen Kkay mice were divided into two groups with 8 in each: diabetes group (KA) and methionine-diet group (KB). C57BL/6 mice were used as normal control (C57). Four months after being treated with two different diets,the mice were sacrificed and serum homocysteine ( Hcy) was assayed with fluorescence polarization immunoassay. Renal pathological change was examined with periodic acid Schiff ( PAS). The expression of MMP-9 protein and mRNA was detected with immunohistochemical staining and reverse transcriptase-PCR respectively. Results It was shown that induction of hyperhomocysteinemia in Kkay mice ( KB) with a diet enriched in methionine aggravated diabetic nephropathy as compared with the KA group (P < 0. 05 ). The expression of MMP-9 protein and mRNA in KB group was also enhanced and the mean positive area of MMP-9 in KB group was higher than that in KA group( 15. 90% vs 11. 14% , P <0. 05). Conclusion The increased level of Hcy could worsen the nephropathy; this may be related to a higher expression of MMP-9.

关 键 词：同型半胱氨酸 KKAY小鼠 糖尿病肾病 基质金属蛋白酶-9 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]