Influence of AT1 receptor blockade on brain-derived neurotrophic factor signaling in hippocampus of mice
10.3969/j.issn.1008-0074.2015.02.02
- VernacularTitle:A T1受体阻断剂对小鼠海马脑源性神经营养因子信号的影响
- Author:
Haiyan JIN
;
Laijiang CHEN
;
Chunbo LI
;
Yingle XU
;
Zhenzhou ZHANG
;
Guozhen LIN
;
Pingjin GAO
;
Jiuchang ZHONG
- Publication Type:Journal Article
- Keywords:
Angiotensin converting enzyme;
Hippocampus;
Brain-derived neurotrophic factor;
Irbesartan
- From:
Chinese Journal of cardiovascular Rehabilitation Medicine
2015;24(2):123-126
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the alteration of brain‐derived neurotrophic factor (BDNF) signaling and the influ‐ence of irbesartan on it in hippocampus of angiotensin‐converting enzyme 2 (ACE2) knock‐out (KO) mice . Meth‐ods:The 10~11‐week ACE2 KO (Ace2/y ) mice received daily treatment with angiotensin II (Ang II) type 1 (AT1) receptor blocker irbesartan (50 mg/kg) or placebo for two weeks. The wild‐type mice (WT ,Ace2+ /y ) were regarded as normal control. Western blotting method was used to measure levels of BDNF and extracellular signal regulated kinase 1/2 (ERK1/2) in the mice hippocampus. Radioimmunoassay was used to measure plasma Ang level in mice . Results :Compared with normal WT control mice ,there were significant down‐regulations of BDNF protein expres‐sion [ (1 ± 0.16) vs .(0.54 ± 0.16)] in hippocampus and plasma Ang‐ (1‐7) level [ (55.6 ± 7.5) pg/ml vs .(42.8 ± 5.8) pg/ml] ,and significant rise in ERK1/2 phosphorylation [ (1 ± 0.28) vs .(1.79 ± 0.29)] in ACE2 KO mice (P<0.01 all). After irbesartan treatment ,there were significant rise in BDNF protein expression (0.88 ± 0.13) in hippocampus and plasma Ang‐ (1‐7) level [(59.4 ± 8.4) pg/ml] ,and significant reduction in ERK1/2 phosphoryla‐tion level (1.33 ± 0.19) in ACE2 KO mice (P<0.05 or <0.01) .Conclusion:There are BDNF protein expression down‐regulation and enhanced ERK1/2 phosphorylation in hippocampus of ACE2 KO mice. AT1 receptor blockade irbesartan can improve Ang‐ (1‐7 ) level and hippocampus BDNF expression , while reducing hippocampus ERK phosphorylation signal in ACE2 KO mice ,suggesting that AT1 receptor blockade possesses certain brain protective effect.
