通窍活血汤调节Nrf2通路对新生大鼠缺血缺氧性脑损伤血管保护及神经功能改善作用研究OACSTPCD

[Objective]To study the vascular protection and neurological improvement effects of Tongqiao Huoxue Decoction on ischemichypoxic brain injury in newborn rats and the regulation of Nrf2 pathway.[Methods]Neonatal rats were randomly divided into normal control group(12 rats)and model group(60 rats).The model of ischemic hypoxic brain injury rats was established by carotid artery ligation method,and the rats were randomly divided into brain injury group,Tongqiao Huoxue Decoction low-dose group,medium-dose group,and high-dose group and ganglioside group,12 rats per group.Tongqiao Huoxue Decoction low-dose,medium-dose and high-dose groups were given Tongqiao Huoxue Decoction by intragastric administration at the dose of 4,8 and 16 g/kg,respectively,ganglioside group was given intraperitoneal injection of ganglioside at the dose of 10 mg/kg,once a day for 14 days.Morris water maze determination of rats in the 90 s target quadrant residence time and the number of cross platform.Enzyme-linked immunosorbent(ELISA)determination of serum sEPCR,sTM,ET-1 level,vascular tissue SOD,MDA and TNF-α level,the brain tissue TNF-α and IL-6,IL-1β level,Hematoxylin-eosin(HE)staining was used to determine histopathological changes in the hippocampus,and real-time quantitative polymerase chain reaction(RT-qPCR)was used to determine mRNA levels of Nrf2,HO-1,JAK2 and STAT3 in the hippocampus.The protein levels of Nrf2,HO-1,JAK2 and STAT3 in the hippocampus were determined by Western Blot.[Results]Compared with normal control group,the target quadrant residence time and the times of crossing the platform of rats in brain injury group were significantly reduced(P＜0.05).SOD level in vascular tissue,mRNA and protein levels of Nrf2 and HO-1 in hippocampus were significantly decreased(P＜0.05).Serum sEPCR,sTM,ET-1 level,vascular tissue MDA and the level of TNF-α,brain tissue TNF-α and IL-6,IL-1β level,hippocampus JAK2 and STAT3 mRNA and protein levels significantly increased(P＜0.05);compared with brain injury group,the target quadrant residence time and the number of crossing the platform of rats in brain injury group were significantly increased in Tongqiao Huoxue Decoction low-dose,medium-dose and high-dose groups and ganglioside group(P＜0.05).And SOD level in vascular tissue,mRNA and protein levels of Nrf2 and HO-1 in hippocampal tissue were significantly increased(P＜0.05);serum sEPCR,sTM,ET-1 level,vascular tissue MDA and the level of TNF-α,brain tissue TNF-α beta and IL-6,IL-1β level,hippocampus JAK2 and STAT3 mRNA and protein levels significantly reduced(P＜0.05),and there was significant difference between different dose groups of Tongqi Huoxue Decoction(P＜0.05).[Conclusion]Tongqiao Huoxue Decoction can significantly inhibit nerve injury and brain tissue inflammation in rats with ischemic hypoxic brain injury,inhibit vascular oxidative stress injury,and play a protective role in brain tissue and blood vessels.The mechanism may be related to the regulation of Nrf2 pathway.