The transcriptional study of tetramethylpyrazine against cerebral ischemia/reperfusion injury in diabetic rats

Shi-lin Yuan; Yu-jia1 Zhou; Xiao Yang; Miao Sun; Qiong Liu; Qing Chang; Chang-chun Hei; Miao Sun; Qing Chang; Xiao Yang

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The transcriptional study of tetramethylpyrazine against cerebral ischemia/reperfusion injury in diabetic rats

Author: Shi-Lin YUAN ¹ ; Yu-Jia1 ZHOU ¹ ; Xiao YANG ¹ ; Miao SUN ² ; Qiong LIU ² ; Qing CHANG ² ; Chang-Chun HEI ² ; Miao SUN ³ ; Qing CHANG ³ ; Xiao YANG ⁴
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1. School of Clinical Medicine, Neuroscience Center, Ningxia Medical University
2. School of Basic Medicine, Ningxia Medical University
3. Key Laboratory of Fertility Preservation and Maintenance (NXMU) Ministry of Education, Ningxia Medical University
4. Ningxia Key Laboratory of Craniocerebral Diseases, Ningxia Medical University
Publication Type:Journal Article
Keywords: cer¬ebral ischemia/reperfusion injury; diabetes mellitus; full-length transcrip¬tome sequencing; inflammatory response; signaling pathway; tetramethylpyrazine
From: Chinese Pharmacological Bulletin 2022;38(11):1688-1698
CountryChina
Language:Chinese
Abstract: Aim To investigate the protective effect of tetramethylpyrazine ( TMP ) on cerebral ischemia/reper¬fusion ( I/R) injury in diabetes mellitus ( DM ) rats based on full-length transcriptome sequencing tech¬nique and the underlying mechanism. Methods The rat model of DM was induced by intraperitoneal injec- tion of streptozotocin (STZ,50 mg • kg" ) . The global cerebral I/R model of rats was established by double vessel occlusion (2-VO) for 10 min and reperfusion for 16 h. TMP (40 mg • kg ) was injected intraperitone-ally every day. Brain water content detection, HE stai¬ning, Nissl staining and TUNEL staining were used to evaluate the neuroprotective effect of TMP on cerebral I/R injury in DM rats. The differentially expressed genes were screened by full-length transcriptome se¬quencing. The possible candidate genes and metabolic pathways of TMP for cerebral ischemia protection in DM rats were screened by functional annotation and metabolic pathway enrichment analysis, and verified by RT-qPCR and Western blot. Results TMP treatment could reduce the degree of brain edema, increase the number of Nissl bodies and neurons, and significantly reduce cell necrosis and apoptosis after cerebral I/R in DM rats. GO enrichment analysis showed that the dif¬ferentially expressed genes after TMP treatment were mainly enriched in biological functions such as inflam¬matory response, transcription factor complex, growth factor activity and so on. KEGG pathway analysis showed that it was mainly concentrated in apoptosis, Toll-like receptor and other signaling pathways. Among them TMP down-regulated genes included TLR2, MyD88, IL-lp, Caspase-3, etc. The results of RT-qPCR and Western blot confirmed that TMP could down-regulate TLR2, MyD88, NF-KB, IL-10, IL-6 and Caspase-3 , and up-regulate the mRNA and protein expression of Bcl-2. Conclusions TMP may amelio¬rate neuronal apoptosis by inhibiting inflammatory re¬sponse, which improves cerebral I/R injury in DM rats, and the pathway may be TLR2/MyD88/NF-KB signaling pathway.