[Protective effect of edaravone on chlorpyrifos-induced brain injury in rats and its mechanism].

Objective: To investigate the protective effect of edaravone on chlorpyrifos-induced neuronal apoptosis and its mitochondrial mechanism. Methods: Under the principle of randomization and double-blindness, the rats were divided into control group, chlorpyrifos group, and edaravone group (n=6). The rats in edaravone group were treated with edaravone (10 mg/1.6 ml/kg, ip.) 1 h after chlorpyrifos injection. After continuous injection of chlorpyrifos and edaravone for 28 days, the learning and memory abilities of the rats were tested by open field and water maze tests. The rat brain tissue was collected after cardiac perfusion, and the neuronal damage in the hippocampus of the brain was detected by HE staining and the mitochondrial and nuclear damage were observed by transmission electron microscopy. The contents of Na+-K+-ATPase and ATP were measured to evaluate mitochondrial damage. The expression of mitochondrial fission protein DRP1 and phosphorylation at Ser 637 of DRP1 were determined by immunohistochemistry and immunoblotting. Results: Compared with the control group, the total movement distance and average speed of the rats in the chlorpyrifos group were decreased significantly within 3 minutes of the open field test (P＜0.01), and the escape latency within 1 minute of the water maze test was prolonged significantly. The number of platform crossings was reduced significantly (P＜0.01), the activity of ATPase in brain tissue was decreased significantly (P＜0.01) , the content of ATP and the phosphorylation level of Ser637 of mitochondrial DRP1 were decreased significantly (P＜0.05, P＜0.01). After edaravone treatment, the total movement distance and average speed of rats in the open field test were increased (P＜0.05), the latency in the water maze test was decreased, and the number of crossing platforms was increased (P＜0.01), brain pathological sections showed that nerve cells were arranged neatly, nucleus and mitochondrial damage was significantly improved, the activity of ATPase in brain tissue was increased (P＜0.01), the levels of ATP and mitochondrial DRP1 Ser637 phosphorylation increased (P＜0.05, P＜0.01).Conclusion: Edaravone alleviates chlorpyrifos-induced brain injury in rats by promoting the phosphorylation of DRP1 at Ser637.

[miR-99b-5p inhibits the activation of NLRP3 inflammasome to alleviate the neurotoxicity induced by paclitaxel chemotherapy].

OBJECTIVE: To study the effects of miR-99b-5p (non-coding RNA) in alleviating pathological neuropathic pain after paclitaxel chemotherapy by inhibiting NLRP3 inflammatory vesicle activation and the effects on neuronal cells pyrosis and apoptosis. METHODS: SD rats were randomly divided into blank group, model group, agomiR-99b-5P treatment group, and agomiR-NC group, 6 rats in each group. The blank group received saline treatment as a control, the model group established a pain model induced by paclitaxel, and the rats in agomiR-99b-5p treatment group and agomiR-NC group were treated with agomiR-99b-5p and agomiR-NC injections, respectively. The expressions of miR-99b-5p in the blank group, model group, and treatment group were detected by RT-qPCR. The mechanical foot retraction threshold (MWT) of the blank group, model group, and treatment group were detected. TUNEL was used to detect the apoptosis of spinal dorsal horn cells. The levels of ROS, MDA, and SOD were detected by ELISA kits. The protein expressions of NLRP3, caspase-1, and IL-1ß were detected by immunofluorescence staining. RESULTS: Compared with the model group, the expression level of miR-99b-5p and the MWT were increased significantly in agomiR-99b-5p treatment group (P＜0.05), the apoptosis of dorsal horn cells was inhibited (P＜0.05), the level of antioxidant stress was increased in rats, the levels of ROS and MDA were decreased (P＜0.05), while the level of SOD was increased (P＜0.05). Immunofluorescence showed that the expressions of NLRP3, caspase-1, and IL-1ß were inhibited by miR-99b-5p. CONCLUSION: miR-99b-5p can alleviate the apoptosis and pyroptosis of neurons after paclitaxel chemotherapy by inhibiting the activation of NLRP3 and improving oxidative stress in vivo.