Neuroprotective effects of stachydrine on hypoxic-ischemic brain damage in neonatal rats by regulating Hippo-YAP signaling pathway
Objective To investigate the neuroprotective effects of stachydrine(STA)on neonatal rats with hypoxic-ischemic brain damage(HIBD)and analyze its mechanism of action.Methods Neonatal SD rats were randomly grouped into sham-operated group,HIBD group,low-,medium-,and high-dose STA groups(5 mg/kg,10 mg/kg,and 20 mg/kg,respectively),and verteporfin(10 mg/kg)+high-dose STA(20 mg/kg)group.Except for the sham-operated group,other rats were applied to establishing HIBD rat models.The neurological deficits of rats in each group were scored,and Morris water maze experiment was performed to evaluate the cognitive function.The brain water content and brain index of rats in each group were measured.HE staining and Nissl staining were used to observe neuronal damage in the brain tissue,TUNEL staining to observe neuronal apoptosis,and Western blot to determine the protein expressions of YES associated protein(YAP),p-YAP,mammalian sterile20-like kinase 1(MST1),p-MST1,and transcriptional coactivator with PDZ-binding motif(TAZ).Results Compared with sham-operated group,the hippocampal tissue damage in HIBD group was aggravated,the number of Nissl bodies decreased(P＜0.05),the neurological deficit score,escape latency,brain tissue water content,brain index,neuronal apoptosis rate,and ratios of p-YAP/YAP and p-MST1/MST1 were significantly higher(P＜0.05),but the platform crossing times and TAZ expression were significantly reduced(P＜0.05).Compared with HIBD group,the hippocampal tissue damage in the low-,medium-,and high-dose STA groups was reduced,the number of Nissl bodies increased(P＜0.05),the neurological deficit score,escape latency,brain tissue water content,brain index,neuronal apoptosis rate,and ratios of p-YAP/YAP and p-MST1/MST1 were significantly lower(P＜0.05),while the platform crossing times and TAZ expression significantly increased(P＜0.05).Compared with high-dose STA group,the hippocampal tissue damage in verteporfin+high-dose STA group was aggravated,the number of Nissl bodies decreased(P＜0.05),the neurological deficit score,escape latency,brain tissue water content,brain index,neuronal apoptosis rate,and ratios of p-YAP/YAP and p-MST1/MST1 were significantly elevated(P＜0.05),but the platform crossing times and TAZ expression were significantly reduced(P＜0.05).Conclusion STA may exert neuroprotective effects on HIBD neonatal rats by regulating Hippo-YAP signaling pathway,reducing neuron damage and neuronal apoptosis,and thus improving the neurological function.
hypoxic-ischemic brain damageneuroprotectionneonatal ratneuronapoptosisstachydrineHippo-YES associated protein signaling pathway
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维普
