洛沙坦降低糖尿病大鼠肾组织膜3型基质金属蛋白酶mRNA的表达  

Losartan reduces the expression of renal membrane type-3 matrix metalloproteinase mRNA in the diabetic rats

作　　者：丁鹤林[1] 徐明彤[1] 陈黎红[1] 黎锋[1] 邓庆丽[2] 王佑民[3] 傅祖植[1] 程桦[1] 钟光恕[1] 

机构地区：[1]中山大学附属第二医院内分泌科,广州510120 [2]中山大学附属第二医院医学研究中心,广州510120 [3]安徽医科大学第一附属医院内分泌科

出　　处：《中华内分泌代谢杂志》2002年第4期264-267,共4页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的　研究洛沙坦对糖尿病大鼠肾组织膜 3型基质金属蛋白酶 (MT3 MMP)mRNA表达的影响。方法　雄性Wistar大鼠分为 3组 ,A组 (11只 )为正常对照组 ,B组 (11只 )为糖尿病未干预组 ,C组 (9只 )为糖尿病大鼠洛沙坦 (血管紧张素Ⅱ 1型受体阻断剂 )干预组。以链脲佐菌素 (STZ)制备糖尿病大鼠模型。大鼠饲养 18周后取出肾脏检测MT3 MMPmRNA表达、电镜检测大鼠肾小球基底膜厚度及系膜基质密度 (系膜基质面积 /系膜面积 ) ;收集 2 4h尿测定尿白蛋白排泄量 (UAE)。mRNA表达采用RT PCR ,以 β actin作为内对照。UAE测定采用大鼠白蛋白特异的酶免疫分析试剂盒。结果　肾组织MT3 MMPmRNA表达在B组大鼠 (1.37± 0 .96 )显著高于A组 (0 .75± 0 .34,P <0 .0 5 )和C组 (0 .75± 0 .30 ,P <0 .0 5 ) ,而后两组比较差异无显著性。UAE、肾小球基底膜厚度及系膜基质密度在B组大鼠均显著高于A组和C组 (P <0 .0 5 )。结论　STZ糖尿病大鼠肾组织MT3 MMPmRNA表达明显增加 ,洛沙坦处理能延缓糖尿病肾病的发生 ,与此同时降低MT3 MMPmRNA表达。提示MT3 MMP与糖尿病肾病发病可能有一定关系。Objective To investigate the effect of Losartan, blocker of angiotensin Ⅱ type 1 receptor, on the expression of renal membrane type 3 matrix metalloproteinase (MT3 MMP) mRNA in the diabetic rats. Methods Male Wistar rats were divided into 3 groups, group A (n=11): control rats, group B (n=11): the diabetic rats without treatment, and group C (n=9): the diabetic rats treated with Losartan. The diabetic model was made by the intraperitoneal injection of streptozotocin. At the end of 18th week, the kidneys were taken out from all the rats to assay the expression of MT3 MMP mRNA by RT PCR and to observe thickness of glomerular basement membrane (GBM) and mesangial matrix (MM) density (MM area/mesangial area) by electron microscope. At the same time, urine was collected for 24 hours to measure urinary albumin excretion (UAE) by rat albumin enzyme immunoassay kit. Results The expression ofrenalMT3 MMPmRNAingroup B (1.37±0.96) was higher than that in group A (0.75±0.34, P<0.05) and group C (0.75±0.30, P<0.05), while no difference between group A and C was found. All the UAE, the GBM thickness and the MM density in group B were significantly higher than those in group A and group C (P<0.05). Conclusion The expression of renal MT3 MMP mRNA is significantly increased in diabetic rats. Losartan in defending the kidney from development of diabetic nephropathy (DN), also reduces the expression of renal MT3 MMP mRNA in diabetic rats, suggesting that MT3 MMP may play a role in the development of DN.

关 键 词：MRNA 实验性糖尿病 糖尿病肾病 洛沙坦 基质金属蛋白酶 逆转录聚合酶链反应 

分 类 号：R587.2[医药卫生—内分泌] R977.15[医药卫生—内科学]