缬沙坦对肾单位不同节段衰老相关基因表达的影响

Effects of valsartan on the expression of aging related gene at different segments of nephron

目的 观察长期抑制肾素 血管紧张素系统 (RAS)对老龄大鼠肾单位不同节段细胞外基质代谢相关调控基因表达的影响。方法 应用自动激光微分离方法分离大鼠肾脏的肾小球及肾小管 ,观察转化生长因子 (TGF β1)和纤维连接蛋白 (FN)的基因表达变化。15月龄大鼠口服缬沙坦(2 5mg/kg)治疗至 2 4月龄 ,与 3月龄及 2 4月龄正常大鼠对比观察TGF β1及FN基因表达的变化。结果 2 4月龄大鼠肾小球及肾小管的TGF β1及FN基因表达较 3月龄大鼠明显增加。缬沙坦治疗对老龄大鼠肾小球的TGF β1mRNA表达无明显影响 ,但明显下调了肾小管的TGF β1、肾小球及肾小管的FNmRNA表达。结论 TGF β1及FN基因表达变化涉及大鼠肾脏肾小球、肾小管的衰老相关性改变 。

Objective To observe the effects of chronic angiotensin Ⅱ blockade on gene expression of extracellular matrix at different segments of nephron in aged rats. Methods Glomeruli and tubules of rat kidney were isolated by laser microdissection and pressure catapulting system. Gene expression level of transforming growth factor (TGF-β 1) and fibronectin (FN) were assessed. Fifteen -month-old male Wistar rats were treated with the valsartan (25mg/kg) until sacrificed at age 24 months, and their TGF-β 1 and FN expression levels were compared with that of young and aged controls. Results Compared with young rats, TGF-β 1 mRNA and FN mRNA expression were both up-regulated in isolated glomeruli and tubules in aged rats. Although Valsartan had no effect on the gene expression of TGF-β 1 in isolated glomeruli, it down regulated TGF-β 1 mRNA in tubules of aged rats. Valsartan also down regulated FN mRNA in both glomeruli and tubules of aged rats. Conclusion The results indicate that changes in TGF-β 1 and FN expression might be involved in the aging related changes of gomeruli and tubules. Activation of RAS at the different segments of nephron in aged rats might regulate the gene expression of ECM through diverse mechanisms.