Regression of nephropathy developed in diabetes by (Pro)renin receptor blockade
Regression of nephropathy developed in diabetes by (Pro)renin receptor blockade
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DOI：
10.1681/asn.2006080820
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发表时间：
2007-07-01
影响因子：
13.6
通讯作者：
Itoh, Hiroshi
中科院分区：
文献类型：
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作者：
Takahashi, Hidena;Ichihara, Atsuhiro;Itoh, Hiroshi
在糖尿病动物中，原肾素受体激活原肾素，刺激组织中的肾素-血管紧张素系统，在肾病的发生发展中起重要作用。本研究检测了（原）肾素受体阻断剂是否能抑制糖尿病大鼠已经发生的肾病进展。17周龄的半肾切除链脲佐菌素诱导的糖尿病大鼠尿蛋白排泄增加和显著的肾小球硬化症，通过皮下植入渗透微型泵，用（原）肾素受体阻滞剂（PRRB）、血管紧张素转换酶抑制剂（ACEi）或载体肽治疗12周。观察结束时，在接受溶剂治疗的糖尿病大鼠中，尿蛋白排泄逐渐增加，并观察到肾小球硬化症显着进展。然而，在糖尿病大鼠与PRRB治疗，没有进一步增加尿蛋白排泄或肾小球硬化症，但12周的治疗与ACEi只衰减进一步增加尿蛋白排泄和肾小球硬化症。在用媒介物处理的糖尿病大鼠的肾脏中观察到活化的原肾素的表达增强，而在用PRRB而不是ACEL处理的糖尿病大鼠的肾脏中其被显著抑制。这些结果表明，（原）肾素受体阻断剂不仅抑制肾病的进展，而且逆转已经在糖尿病大鼠中发展的肾小球硬化。
Activation of prorenin by (pro)renin receptor stimulates the tissue renin-angiotensin system and plays a significant role in the development of nephropathy in diabetic animals. This study examined whether (pro)renin receptor blockade inhibits the progression of nephropathy that has already developed in diabetic rats. Seventeen-week-old heminephrectomized streptozotocin-induced diabetic rats with an increased urinary protein excretion and a significant glomerulosclerosis had been treated for 12 wk with the (pro)renin receptor blocker (PRRB), angiotensin-converting enzyme inhibitor (ACEi), or vehicle peptide by using subcutaneously implanted osmotic minipumps. At the end of observation, in diabetic rats that were treated with vehicle, urinary protein excretion was progressively increased and a significant progression of glomerulosclerosis was observed. In diabetic rats that were treated with PRRB, however, no further increase in urinary protein excretion or glomerulosclerosis was observed, but 12-wk treatment with ACEi only attenuated further increases in urinary protein excretion and glomerulosclerosis. The enhanced expression of activated prorenin was observed in the kidneys of diabetic rats that were treated with vehicle, whereas it was markedly suppressed in the kidneys of diabetic rats that were treated with PRRB but not ACEL These results suggest that (pro)renin receptor blockade does not only inhibit the progression of nephropathy but also reverses the glomerulosclerosis that has already developed in diabetic rats.