Study of influence of ACE2 on glomerular podocytes in diabetic rats and the effects of irbesartan

Objective To observe the effects of the renal local angiotensin-converting enzyme 2 (ACE2) expressions on glomerular podocytes in diabetic rat and the function of irbesartan.Methods Fifty-six Wistar rats were induced diabetes by streptozotocin,nine were dead.The others were randomly divided into diabetes group (n =11),hydralazine administrated group (n =9),25 mg · kg-1 · d-1 irbesartan administrated group(n =9),50 mg · kg-1 · d-1 irbesartan administrated group(n =9),and 200 mg · kg-1 · d-1irbesartan administrated group(n =9),meanwhile normal control group were established (n =7).Four weeks after modeling,rats were administered with hydralazine or irbesartan separately.In the 12th week,24 hour urinary albumin excretion rate(UEAR) was measured.The distribution and expression of ACE2 in renal tissue were detected by immunohistochemistry.The renal glomerulus WT1 expression was detected by streptavidinperosidase(SP).Podocytes density was detected by Image.Pro Plus 6.0.Results The UAER in normal control group was lower than that in diabetes group and all the drug intervention groups (including hydralazine administrated group,25 mg · kg-1 · d-1 irbesartan administrated group,50 mg · kg-1 · d-1irbesartan administrated group,and 200 mg · kg-1 · d-1 irbesartan administrated group) (P ＜0.001).The UAER in all the drug intervention groups were lower than that in diabetes group(P ＜0.001).And in all the irbesartan administrated groups UAER were lower than that in hydralazine administrated group (P ＜ 0.0 5).In 50 mg · kg-1 · d-1 irbesartan administrated group and 200 mg· kg-1 · d-1 irbesartan administrated group,UAER were lower than that in 50 mg · kg-1 · d-1 irbesartan administrated group (P ＜ 0.001).The level of renal ACE2 was positively correlated with podocytes density(r =0.381,P ＜ 0.001).And it was significantly lower in diabetes group than that in normal control group(P ＜0.05).In all the irbesartan administrated groups,the levels of ACE2 were significantly higher than that in diabetes group and hydralazine administrated group(P ＜ 0.001).Podocytes density in all the irbesartan administrated groups and hydralazine administrated group were significantly higher than that in diabetes group(P ＜0.001).Podocytes density in 200 mg · kg-1 · d-1 irbesartan administrated group was significantly higher than that in hydralazine administrated group,25 mg · kg-1 · d-1 irbesartan administrated group,and 50 mg · kg-1 · d-1 irbesartan administrated group.Conclusions The reduction of renal local ACE2 expressions leads to reduction of the podocytes,and kidney damage.Irbesartan upregulates renal local ACE2 expressions and increases podocytes density.Irbesartan protects the kidney in dose-dependent manner,besides lowering blood pressure. Key words: Diabetes mellitus;  Glomerular podocytes ;  Angiotensin-converting enzyme 2 ;  Urinary albumin excretion rate