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Published on: October 5, 2012
miR-128b Promotes Cerebral Infarction by Regulating the Expressions of BCL-2 and CAPASE3
Jin Ma1, Lei Bao1, Xiaohua Xia1
1Department of Emergency Medicine, The First People's Hospital of Kunshan, Kunshan City, Jiangsu Province, China.
Objective:
To investigate the effect of miR-128b on apoptosis and BCL-2 and CAPASE3 expression in a rat middle cerebral artery occlusion (MCAO) model.
Methods:
The MCAO model was established by the thread embolism method. miR-128b agomir and antagomir were injected into the ventricle of MCAO rats by stereotaxic intracerebral injection. Then the rats were divided into a sham group, model group, miR-128b agomir group, and miR-128b antagomir group. Zea Longa was used to score the modeling rats. The area of cerebral infarction was assessed by 2,3,5-triphenyltetrazolium chloride staining. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The miR-128b relative expression was detected by real-time polymerase chain reaction. The expressions of BCL-2 and CAPASE3 were detected by immunohistochemistry and Western blotting.
Results:
The MCAO model was constructed successfully. The expressions of miR-128b in the MCAO groups were higher than that of the sham group (P < 0.05). Compared with the model group, the cerebral infarction area in the miR-128b agomir group was significantly bigger and that of the miR-128b antagomir group was smaller (P < 0.05). The number of apoptotic cells in the miR-128b agomir group was more and that of miR-128b antagomir group was less (P < 0.05 vs. model group). The BCL-2 expression reduced and CAPASE3 expression increased in the MCAO groups (P < 0.05 vs. sham group). Compared with the model group, the Bcl-2 expression decreased and Caspase 3 expression increased in the miR-128b agomir group, and those in the miR-128b antagomir group were opposite.
Conclusions:
miR-128b promoted cerebral infarction in MCAO rats by regulating Bcl-2 and Caspase 3 expression.
Insights
MicroRNA-128b (miR-128b) exacerbates stroke damage in rats by increasing brain infarction and apoptosis. Inhibiting miR-128b offers a potential therapeutic strategy for middle cerebral artery occlusion (MCAO) by reducing these effects.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Middle cerebral artery occlusion (MCAO) is a common cause of ischemic stroke.
- MicroRNAs (miRNAs) play crucial roles in regulating cellular processes, including apoptosis.
- The specific role of miR-128b in MCAO-induced brain injury requires further elucidation.
Purpose of the Study:
- To investigate the impact of miR-128b on apoptosis and related protein expression in a rat MCAO model.
- To explore the potential of modulating miR-128b for therapeutic intervention in ischemic stroke.
Main Methods:
- Established a rat MCAO model using the thread embolism technique.
- Administered miR-128b agomir or antagomir via stereotaxic intracerebral injection.
- Assessed neurological deficits, cerebral infarction volume, apoptosis, and protein expression (BCL-2, Caspase-3) using established assays.
Main Results:
- miR-128b expression was significantly upregulated in MCAO rats compared to sham controls.
- Overexpression of miR-128b (agomir) increased cerebral infarction area and apoptosis.
- Inhibition of miR-128b (antagomir) reduced infarction and apoptosis, accompanied by altered BCL-2 and Caspase-3 expression.
Conclusions:
- miR-128b promotes cerebral infarction and apoptosis in MCAO rats.
- The mechanism involves the regulation of BCL-2 and Caspase-3 protein expression.
- Targeting miR-128b presents a promising therapeutic avenue for ischemic stroke.
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