Conclusion
BMSC-EVs carried miR-183-5p into db/db-ICH rat brain tissues and repressed the NLRP3 pathway by targeting PDCD4, thus alleviating neuroinflammation after diabetic ICH.
Methods
BMSC-EVs were isolated and identified. The rat model of db/db-ICH was established and the model rats were administered with EVs. miR-183-5p expression in brain tissues of db/db-ICH rats was detected. The brain injury of db/db-ICH rats was evaluated by measuring neurobehavioral score, brain water content and inflammatory factors. BV2 cells were cultured in vitro to establish high-glucose (HG)-Hemin-BV2 cell model. The levels of reactive oxygen species (ROS) and inflammatory factors in BV2 cells were measured, and BV2 cell viability and apoptosis were assessed. The targeting relationship between miR-183-5p and PDCD4 was predicted and verified. The activation of PDCD4/NLRP3 pathway in rat brain tissues and BV2 cells was detected.
Results
miR-183-5p expression was reduced in db/db-ICH rats brain tissues. BMSC-EVs ameliorated cranial nerve function, decreased brain water content and repressed inflammatory response by carrying miR-183-5p. BMSC-EVs mitigated HG-Hemin-BV2 cell injury, reduced ROS level and suppressed inflammatory response. miR-183-5p targeted PDCD4. PDCD4 promoted BV2 cell inflammation by activating the NLRP3 pathway. BMSC-EVs inhibited HG-Hemin-BV2 cell inflammation through the miR-183-5p/PDCD4/NLRP3 pathway, and inhibition of miR-183-5p reversed the protective effect of EVs.