| Objective: To investigate the effect of angiotensinⅡ (AngⅡ) type1receptorblocker(ARB) on12-lipoxygenase(12-LO) activaton and P-cadherin expression in type2diabetic nephropathy rat glomeruli.Methods:(1)12(S)-HETE was infused to rats by osmotic mini-pump.Rats fed high fatdiet were received low dose streptozotocin（STZ） to make type2diabetes and divided into2groups: low dose STZ(DN group), low dose STZ+ARB treatment(ARB group). Rats fedregular chow were as control group（Ctrl group）.All rats were sacrificed after6weeks. Urine,blood, kidney cortical tissue and isolated glomeruli by sieving method were collected at theend of study respectively. ELISA and Western blot for related target were performedrespectively.(2)Type2diabetic patients were receive ARB treatment,at the beginning of thetreatment and after the treatment,we collected the blood glucose、BUN、Scr、24-hour urinaryprotein respectively,IF for detecting the podocyte P-cadherin protein.Results:(1)P-cadherin protein expression in the glomeruli were significantly decreasedby12(S)-HETE stimulation(P<0.01).Blood glucose (P<0.01),kidney/body weight (P<0.01)and24hour urinary protein(P<0.01) were increased in DN group compared withCtrl.However, urine protein(P<0.05)，Kidney/body weight(P<0.05) were decreased in ARBgroup compared with DN group.Increment of12（S）-HETE content(P<0.01) and decrementof P-cadherin expression(P<0.01) were observed in DN glomeruli compared with Ctrl(P<0.01).These abnormalities were prevented by administration of the ARB(P<0.05).(2)After ARB treatment,24hour urinary protein and urine podocyte P-cadherin weredecreased.Before ARB treatment, urine podocyte P-cadherin were increased by ELISA andWestern blot.Conclusions: AngⅡ can downregulate glomeruli P-cadherin expression via activationof12-LO. ARB can ameliorate the progression of DN via upregulation of glomeruliP-cadherin through inhibition of12-LO activation in type2DN. |
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