Effect of angiotensin Ⅱ type 1 receptor blocker on the 12-lipoxygenase activity and P-cadherin expression in type 2 diabetic rat glomeruli
10.3760/cma.j.issn.1001-7097.2013.03.010
- VernacularTitle:血管紧张素Ⅱ1型受体拮抗剂对糖尿病肾病大鼠肾小球内12-脂氧合酶活性及P钙黏蛋白表达的影响
- Author:
Wanning WANG
;
Jia LI
;
Fuzhe MA
;
Tao SUN
;
Mindan SUN
;
Zhonggao XU
- Publication Type:Journal Article
- Keywords:
Angiotensin Ⅱ type 1 receptor blockers;
Diabetic nephropathies;
Lipoxygenase;
Angiotensin Ⅱ;
Cadherin
- From:
Chinese Journal of Nephrology
2013;(3):210-215
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of angiotensin Ⅱ (Ang Ⅱ) type 1 receptor blocker (ARB) on 12-lipoxygenase (12-LO) activity and P-cadherin expression in type 2 diabetic rat glomeruli.Methods Podocytes were stimulated by 107 mol/L Ang Ⅱ for 24 hours.12(S)-HETE (1mg· kg 1 · d-1) and Ang Ⅱ (400 ng· kg-1· min-1) were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively.Rats fed with high fat diet received low dose streptozotocin (STZ) to make type 2 diabetes and divided into 2 groups:low dose STZ (DN group),low dose STZ + ARB treatment (Losartan group).Rats fed with regular chow were used as control group.All the rats were sacrificed after 6 weeks.Urine,blood,kidney cortical tissue and isolated glomeruli by sieving method were collected at the end of study respectively.ELISA,RT-PCR and Western blotting for related target were performed respectively.Results Ang Ⅱ increased 12(S)-HETE levels in podocytes and glomeruli (all P ＜ 0.01).Ang Ⅱ levels in the glomeruli were significantly increased by 12(S)-HETE stimulation (P ＜0.01).Blood glucose,kidney/body weight and 24 hour urinary protein were increased in DN group compared with that in control group (all P ＜ 0.01).However,urine protein,Kidney/body weight were decreased in Losartan group compared with DN group (all P ＜ 0.05).Increment of 12(S)-HETE content and decrement of P-cadherin expression were observed in DN glomeruli compared with that in control group(all P ＜ 0.01).These abnormalities were prevented by administration of the losartan (all P ＜ 0.05).Conclusions Ang Ⅱ can down-regulate glomerular P-cadherin expression via activation of 12-LO.ARB can ameliorate the progression of DN via up-regulation of glomerular P-cadherin through inhibition of 12-LO activation in type 2 DN rats.
