Isoflurane-induced expression of miR-140-5p aggravates neurotoxicity in diabetic rats by targeting SNX12
| Autor: | Lukun Yang, Simin Yang, Ru Zhang, Yuxiang Han, Dongyi Fan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Gene Expression Morris water navigation task 010501 environmental sciences Pharmacology Toxicology 030226 pharmacology & pharmacy 01 natural sciences Neuroprotection Streptozocin Diabetes Mellitus Experimental Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Diabetes mellitus medicine Animals Sorting Nexins 0105 earth and related environmental sciences Gene knockdown Isoflurane business.industry Neurotoxicity medicine.disease Streptozotocin MicroRNAs Apoptosis Anesthetics Inhalation business medicine.drug |
| Zdroj: | The Journal of Toxicological Sciences. 45:69-76 |
| ISSN: | 1880-3989 0388-1350 |
| Popis: | MicroRNAs (miRNAs) are widely known as critical regulators in isoflurane-induced neurotoxicity during the development of brain. Moreover, isoflurane could aggravate cognitive impairment in diabetic rats. The present study was designed to investigate the role and mechanism of miR-140-5p on isoflurane-induced neurotoxicity in diabetic rats. Firstly, a diabetic rat model was established by injection of streptozotocin (STZ) and identified by Morris water maze test. The result indicated that isoflurane treatment exacerbated STZ-induced cognitive impairment, as demonstrated by increase of the latency to the platform and decrease of the proportion of time spent in the target quadrant. Secondly, miR-140-5p was up-regulated in diabetic rats treated with isoflurane. Functional assays revealed that knockdown of miR-140-5p attenuated neurotoxicity in diabetic rats, which was shown by a decrease of the latency to the platform and an increase of the proportion of time spent in the target quadrant. Mechanistically, we demonstrated that miR-140-5p directly bonded to SNX12 (sorting nexin 12). At last, the neuroprotective effect of miR-140-5p knockdown against isoflurane-aggravated neurotoxicity in diabetic rats was dependent on up-regulation of SNX12 and inhibition of cell apoptosis. In summary, these meaningful results demonstrated the mitigation of miR-140-5p knockdown against isoflurane-aggravated neurotoxicity in diabetic rats via SNX12, suggesting a novel target for neuroprotection in diabetes under isoflurane treatment. |
| Databáze: | OpenAIRE |
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