Abstract
Neuroprotective Effects of Tetramethylpyrazine-Mediated Nuclear Factor Erythroid 2-Related Factor 2 Regulation on AIM 2 Inflammasome in Ischemic Stroke and Reperfusion Injury
Department of Brain Disorders, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, Chaoyang 530021, China
Correspondence Address:
F. Xu, Department of Brain Disorders, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, Chaoyang 530021, China, E-mail: xufeng1666@163.com
This study aims to construct a rat model to observe the neuroprotective effect of tetramethylpyrazine during the process of ischemic stroke reperfusion and further explore the mechanism of nuclear factor erythroid 2 related factor 2 regulation of absent in melanoma 2 inflammasome on brain neurons, providing a basis for clinical treatment. Experimental rats were grouped into a model control group, tetramethylpyrazine group, nuclear factor erythroid 2 related factor 2 inhibitor (ML385) group, tetramethylpyrazine+ML385 group and healthy group. Neurological function and brain tissue water content were compared between the groups. Additionally, the infarct area in the brain, neuronal apoptosis, levels of B cell lymphoma-2 and B cell lymphoma-2-associated protein X were observed by triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling and enzyme-linked immunosorbent assays respectively. Quantitative polymerase chain reaction and immunoblotting were adopted to study the levels of absent in melanoma 2 and nuclear factor erythroid 2 related factor 2 in brain tissues. On the 3rd and 7th d after modeling, modified neurological severity score behavioral scores denoted least in tetramethylpyrazine group and highest in ML385 group. Brain tissue water content analysis showed that tetramethylpyrazine rats had significantly higher brain tissue water content than the healthy group but significantly lower in other rats. ML385 group had the highest brain tissue water content. Triphenyltetrazolium chloride staining indicated that there was a white infarct area in the left cerebral cortex and striatum of controls, tetramethylpyrazine rats showed significantly less infarct area. ML385 group had a significantly increased infarct rate, while tetramethylpyrazine+ML385 group showed a drastically lower infarct rate than ML385 rats but higher than the tetramethylpyrazine group. Similarly, hippocampal cornu ammonis 1, quantitative polymerase chain reaction and immunoblotting results were also studied. Tetramethylpyrazine can promote nuclear factor erythroid 2-related factor 2 expression downregulates absent in melanoma 2 levels and reduce neuronal cell apoptosis in brain tissue, which is related to its inhibition of brain tissue inflammatory responses. This could indicate a novel therapeutic direction for treating cerebral ischemic reperfusion injury.
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