Temporary angiotensin II blockade at the prediabetic stage attenuates the development of renal injury in type 2 diabetic rats
Temporary angiotensin II blockade at the prediabetic stage attenuates the development of renal injury in type 2 diabetic rats
复制标题
DOI：
10.1681/asn.2004080649
复制
发表时间：
2005-03-01
影响因子：
13.6
通讯作者：
Nishiyama, A
中科院分区：
文献类型：
--
作者：
Nagai, Y;Yao, L;Nishiyama, A
研究了糖尿病前期阶段暂时性血管紧张素II（AngII）阻断是否减轻2型糖尿病OLETF大鼠日后的肾损伤。OLETF大鼠在糖尿病前期阶段（4至11周龄）接受AT 1受体拮抗剂（奥美沙坦，食物中0.01%）、血管紧张素转换酶抑制剂（替莫普利，食物中0.01%）、两者的组合或肼苯哒嗪（25 mg/kg/d）治疗，然后在不进一步治疗的情况下进行监测，直至50周龄。在11周龄时，OLETF和对照LETO大鼠的血糖水平和尿蛋白排泄量（U蛋白V）相似。然而，OLETF大鼠肾脏血管紧张素Ⅱ含量和IV型胶原mRNA表达高于LETO大鼠在这个年龄。奥美沙坦、替莫普利及其联合用药可降低这些风险，但肼苯哒嗪未降低这些风险。在50周龄时，糖尿病OLETF大鼠的血压、尿蛋白V和肾内血管紧张素II水平高于LETO大鼠。暂时性血管紧张素II阻断不影响OLETF大鼠的葡萄糖代谢或高血压的发展，但显着抑制蛋白尿和改善肾小球损伤。然而，临时肼苯哒嗪治疗未影响任何参数。目前的研究表明，肾内血管紧张素II和IV型胶原蛋白的表达已经增加了糖尿病变得明显之前很久在OLETF大鼠。此外，在糖尿病前期阶段暂时性AngII阻断减弱了这些动物中肾损伤的进展。这些数据表明，早期血管紧张素Ⅱ阻滞可能是一种有效的策略，以防止2型糖尿病肾损伤的发展以后的生活。
Whether temporary angiotensin II (AngII) blockade at the prediabetic stage attenuates renal injury in type 2 diabetic OLETF rats later in life was investigated. OLETF rats were treated with an AT, receptor antagonist (olmesartan, 0.01% in food), angiotensin-converting enzyme inhibitor (temocapril, 0.01% in food), a combination of the two, or hydralazine (25 mg/kg per d) at the prediabetic stage (4 to 11 wk of age) and then monitored without further treatment until 50 wk of age. At 11 wk of age, blood glucose levels and urinary protein excretion (UproteinV) were similar between OLETF and control LETO rats. However, OLETF rats showed higher kidney AngII contents and type IV collagen mRNA expression than LETO rats at this age. These decreased with olmesartan, temocapril, and a combination of these but not with hydralazine. At 50 wk of age, diabetic OLETF rats showed higher BP, UproteinV, and intrarenal AngII levels than LETO rats. Temporary AngII blockade did not affect glucose metabolism or the development of hypertension in OLETF rats but significantly suppressed proteinturia and ameliorated glomerular injury. However, no parameters were affected by temporary hydralazine treatment. The present study demonstrated that intrarenal AngII and type IV collagen expression are already augmented long before diabetes becomes apparent in OLETF rats. Furthermore, temporary AngII blockade at the prediabetic stage attenuates the progression of renal injury in these animals. These data suggest that early AngII blockade could be an effective strategy for preventing the development of type 2 diabetic renal injury later in life.