Dynamic expressions of miR-34a and related target genes sirtuin 1 and nuclear factor-E2-related factor 2 and their significances in subependymal zone of rats with cerebral ischemia
10.3760/cma.j.issn.1671-8925.2019.05.003
- VernacularTitle:脑缺血后大鼠室管膜下区miR-34a及其相关靶基因Sirt1、Nrf2的动态表达及意义
- Author:
Wei LIAO
1
;
Leiying ZHANG
;
Peng LIU
;
Liansheng ZOU
;
Jianyun LOU
;
Shaochun YANG
Author Information
1. 赣南医学院第一附属医院神经外科
- Keywords:
Cerebral ischemia;
MiR-34a;
Sirtuin l;
Nuclear factor-E2-related factor 2;
Neural stem cell;
Cell proliferation
- From:
Chinese Journal of Neuromedicine
2019;18(5):447-452
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the expression changes ofmiR-34a and its related target genes sirtuin 1 (Sirtl) and nuclear factor-E2-related factor 2 (Nrf2) in subependymal zone (SVZ) of rats after cerebral ischemia,and to explore the effect of miR-34a on proliferation of endogenous neural stem cells (NSCs) after cerebral ischemia.Methods Forty SD rats were randomly divided into control group,cerebral ischemia one d group,cerebral ischemia three d group and cerebral ischemia 7 d group (n=10).Middle cerebral artery occlusion models were established by thread embolization in the latter three groups,and the SVZs were taken one,three and 7 d after model making,respectively.Immunofluorescence staining was used to detect the expression of nestin,real-time PCR was used to detect the mRNA expressions ofmiR-34a,Sirtl and Nrf2,and Western blotting was used to detect the protein expressions of Sirt1 and Nrf2.Results (1) In SVZs of cerebral ischemia one d group,cerebral ischemia three d group and cerebral ischemia 7 d group,the number of nestin positive cells increased gradually ([2.013±0.526],[4.821 ±1.154],and [6.394±1.027]) cells/filed,with statistical differences (P＜0.05).(2) In SVZs of cerebral ischemia one d group,cerebral ischemia three d group and cerebral ischemia 7 d group,the expression levels of miR-34a mRNA increased gradually (0.295±0.145,0.701 ±0.075,and 1.136±0.018),the Sirt1 mRNA expression levels showed a downward trend (0.835±0.024,0.620±0.133,and 0.278±0.110),the Nrf2 mRNA expression levels obviously decreased (1.032±0.256,0.833±0.187,and 0.630±0.123),the Sirt1 protein expression levels showed a downward trend (0.832±0.018,0.731±0.156,and 0.454±0.132),and the Nrf2 protein expression levels obviously decreased (1.003±0.133,0.813±0.111,and 0.671 ±0.071),with statistically significant differences (P＜0.05).(3)Statistical correlation analysis showed that the number of nestin positive cells was positively correlated with miR-34a mRNA expression level and negatively correlated with Sirt1 and Nrf2 mRNA and protein expression levels after cerebral ischemia (r=0.887,P=0.003;r=-0.746,P=0.005;r=-0.521,P=0.013;r=-0.344,P=0.025;r=-0.863,P=0.000).Conclusions MiR-34a may regulate the proliferation of NSCs through Sirt1/Nrf2 pathway after cerebral ischemia.
