PMID- 31599430
OWN - NLM
STAT- MEDLINE
DCOM- 20201006
LR  - 20201006
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 18
DP  - 2019 Sep
TI  - Influence of miR-34a on cerebral neuronal apoptosis in rats with cerebral 
      ischemia reperfusion through the Notch1 signaling pathway.
PG  - 8049-8057
LID - 19021 [pii]
LID - 10.26355/eurrev_201909_19021 [doi]
AB  - OBJECTIVE: To explore the influence and the underlying mechanism of 
      micro-ribonucleic acid (miR)-34a on cerebral neuronal apoptosis in rats with 
      cerebral ischemia-reperfusion (CIR). MATERIALS AND METHODS: 60 adult male Wistar 
      rats were randomly divided into 3 groups: Sham group, CIR group and miR-34a 
      knockdown group. The rat model of CIR was established using the suture occlusion 
      method. The expression level of miR-34a in lesion tissues in the three groups was 
      determined via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The 
      pathological injury of brain tissues was detected via hematoxylin-eosin (HE) 
      staining and the infarction region in each group was evaluated via triphenyl 
      tetrazolium chloride (TTC) staining. The terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to 
      measure the cerebral neuronal apoptosis level. The level of Nissl's body in each 
      group was detected via Nissl's staining. The expression level of the 
      platelet-derived neurotrophic factor (PDNF) and Notch1/hypoxia-inducible 
      factor-1alpha (HIF-1alpha) signaling pathway-related proteins in brain tissues were 
      detected via immunohistochemistry and Western blotting, respectively. RESULTS: 
      The expression level of miR-34a in brain tissues of the CIR group was 
      significantly increased compared to that of the Sham group (p < 0.05). After the 
      intervention with miR-34a, the infarction area of brain tissues was markedly 
      reduced when comparing to the CIR group (p < 0.05). In addition, the results of 
      HE staining and Nissl staining revealed that CIR treatment led to edema in 
      cerebral neurons, disorderly arranged neurons, and remarkably decreased number of 
      Nissl's bodies. However, miR-34a knockdown following CIR significantly alleviated 
      the brain tissue injury and markedly increased the number of Nissl's bodies (p < 
      0.05). The results of TUNEL staining also indicated that miR-34a siRNA could 
      remarkably reverse the cerebral neuronal apoptosis caused by CIR in rats (p < 
      0.05). According to the immunohistochemical staining results, the expression of 
      PDNF in brain tissues declined in the CIR group, while enhanced in the miR-34a 
      siRNA group (p < 0.05). Furthermore, the Western blotting results manifested that 
      miR-34a siRNA could up-regulate the Notch1 and HIF-1alpha protein expressions in 
      brain tissues of CIR rats. CONCLUSIONS: Our data demonstrated that the miR-34a 
      knockdown could alleviate the brain tissue injury and neuronal apoptosis by 
      activating the Notch1/HIF-1alpha signaling pathway CIR-treated rats.
FAU - Wang, S-P
AU  - Wang SP
AD  - Department of Neurological Rehabilitation, the Third People's Hospital of 
      Qingdao, Qingdao, China. ibsr96@163.com.
FAU - Wang, D
AU  - Wang D
FAU - Li, H-X
AU  - Li HX
FAU - Liu, L
AU  - Liu L
FAU - Duan, X-H
AU  - Duan XH
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN34 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Notch1 protein, rat)
RN  - 0 (Receptor, Notch1)
SB  - IM
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Brain Ischemia/genetics/metabolism/pathology
MH  - Gene Knockdown Techniques
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Infarction, Middle Cerebral Artery/*genetics/metabolism/pathology
MH  - MicroRNAs/*genetics
MH  - Nerve Growth Factors/metabolism
MH  - Neurons/*metabolism
MH  - Rats
MH  - Receptor, Notch1/*metabolism
MH  - Reperfusion Injury/*genetics/metabolism/pathology
MH  - Signal Transduction
EDAT- 2019/10/11 06:00
MHDA- 2020/10/07 06:00
CRDT- 2019/10/11 06:00
PHST- 2019/10/11 06:00 [entrez]
PHST- 2019/10/11 06:00 [pubmed]
PHST- 2020/10/07 06:00 [medline]
AID - 19021 [pii]
AID - 10.26355/eurrev_201909_19021 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):8049-8057. doi: 
      10.26355/eurrev_201909_19021.