Effect of aging and hypertension on renal cortex angiotensin Ⅱ expression and podocyte autophagy in rats
10.3760/cma.j.issn.0254-9026.2016.04.018
- VernacularTitle:衰老和高血压对大鼠肾皮质血管紧张素Ⅱ及肾小球足细胞自噬的影响
- Author:
Mingjiao PAN
;
Mengyun XIAO
;
Yang LYU
;
Bo FU
;
Lu YU
;
Xiaodan WANG
- Publication Type:Journal Article
- Keywords:
Aging;
Hypertension;
Angiotensin Ⅱ;
Podocytes;
Autophagy
- From:
Chinese Journal of Geriatrics
2016;35(4):421-426
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the changes of renal cortex angiotensin Ⅱ (AngⅡ) expression and podocyte autophagy in aging rats with normotension versus hypertension,to further investigate the possible mechanism of renal injury in hypertension during aging.Methods Normotensive Wistar-Kyoto-rats (WKYs) were allocated to three groups by age of 3-month-old group,13-month-old group,22-month-old group.Gender,age and number-matched spontaneously hypertensive rats (SHRs) served as controls.Blood pressure was monitored.Levels of urinary albumin,urinary creatinine,serum creatinine (SCR),blood urea nitrogen (BUN),Ang Ⅱ in serum and in renal cortex were detected.The kidney ultrastructural changes and podocyte autophagosomes were observed under light and transmission electron microscopy.Expressions of nephrin,LC3B Ⅱ,Atg5 and p62 in glomeruli were analyzed by Western blotting.Results Blood pressure was significantly higher in SHRs than in WKYs (P＜0.05).During aging from 3-month-old to 13-month-old and to 22 monthold group,the urinary albumin/creatinine ratio was increased significantly in SHRs with hypertension and in WKYs with normotension [WKY:(0.12±0.01) g/mmol,(0.14±0.04) g/mmol vs.(0.34± 0.05) g/mmol;in SHR:(0.29±0.04) g/mmol,(0.31±0.05) g/mmol vs.(0.72±0.16) g/mmol,P＜0.05],but SCR and BUN levels had no significant difference in SHRs and WKYs during aging (both P＞0.05).And Ang Ⅱ levels in both serum and renal cortex had no significant change in normotension group during aging three time points (both P＞0.05).An age-dependent decrease of Ang Ⅱ level in renal cortex appeared during aging three time points in hypertensive rats [SHR:(0.02 ±0.00) μg/L,(0.02±0.00) μg/L vs.(0.01±0.00) μg/L,P＜0.05],but serum level of Ang Ⅱ had no significant difference during aging three time points (P＞ 0.05) in hypertension group.The structural changes,including glomerulosclerosis,tubular atrophy and interstitial fibrosis were observed during aging three time points both in normotensive and hypertensive rats,but these pathological changes were more serious in hypertensive rats.Autophagosomes relatively accumulated in aging normotensive rats.The protein expressions of LC3B Ⅱ,Atg5 and p62 were increased in normotensive rats during aging (all P＜0.05).While the protein expressions of nephrin,LC3B Ⅱ,Atg5 and p62 were decreased in aging hypertensive rats (all P ＜ 0.05).Conclusions Ang Ⅱ expression level in renal cortex is decreased during aging in hypertensive rats.Podocyte autophagic activity is relatively decreased during aging in normotensive rats,but is relatively increased during aging in hypertensive rats.Ang Ⅱ-induced podocyte autophagy may be involved in the pathogenesis of renal injury in hypertension during aging.
