Effects and mechanism of gastrodin on labor analgesia in rats and on hypoxic-ischemic brain injury in neonatal rats
Objective To investigate the effects of gastrodin(GAS)on labor analgesia in rats and on hypoxic-ischemic brain injury in neonatal rats and its possible mechanism.Methods Sixty pregnant rats were randomly divided into blank group,low,medium and high dose of GAS groups and positive control group,with 12 rats in each group.After the beginning of labor,50,100 and 150 mg·kg-1 GAS(prepared with normal saline)was injected intraperitoneally in the low,medium and high dose of GAS group,remifentanil hydrochloride 5 μg·kg-1 was injected into the tail vein of the positive control group,and same amount of normal saline was given to the blank group.The pain threshold of delivery was measured by hot water tail flicking method.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)was detected by enzyme linked immunosorbent assay(ELISA).The mRNA and protein expressions of nuclear factors-κB p65(NF-κB p65),phosphorylated nuclear factors-κB p65(p-NF-κB p65)and NOD like receptor protein 3(NLRP3)in rat hippocampus were detected by quantitative real-time polymerase chain reaction(RT-qPCR)and Western blotting.The learning and memory ability of neonatal rats was evaluated by Morris water maze test.The pathological changes of hippocampal CA1 area of rats were observed by HE staining.The brain water content of neonatal rats was measured.Results Compared with the blank group,the pain threshold and neonatal rat number of crossing platform were increased,the levels of TNF-α,IL-1β,IL-6,and p-NF-κB p65 protein expression,NF-κB p65 mRNA expression,NLRP3 mRNA and protein,neonatal rat escape latency and brain water content were decreased in low,medium and high dose of GAS group and positive control group(P<0.05).Compared with the low dose of GAS group,the TNF-α,IL-1β,IL-6,and p-NF-κB p65 protein expression,NF-κB p65 mRNA expression,NLRP3 mRNA and protein,neonatal rat escape latency and brain water content were decreased in medium and high dose of GAS group and positive control group(P<0.05).Compared with the medium dose of GAS group,the TNF-α,IL-1β,IL-6,and p-NF-κB p65 protein expression,NF-κB p65 mRNA expression,NLRP3 mRNA and protein,neonatal rat escape latency and brain water content were decreased in high dose of GAS group and positive control group(P<0.05).Compared with the positive control group,there was no significant difference in the above indexes(P>0.05).Conclusion GAS can reduce the sensitivity to pain,reduce the expression of proinflammatory factors,improve neuroinflammation and reduce brain injury in neonatal rats,possibly by inhibiting NF-κB/NLRP3 signaling pathway.
labor analgesiaischemic hypoxic brain injurygastrodinnuclear factor-κBNOD like receptor protein 3