Mechanism of Pinggan Huoxue mixture on cerebral ischemia reperfusion injury based on the NF-κB pathway
Objective To determine the mechanism of Pinggan Huoxue mixture on cerebral ischemia-reperfusion injury(CIRI).Methods CIRI model was induced by suture-occlusion method.SD rats were randomly divided into a sham operation group,a model group,Pinggan Huoxue mixture low-dose,medium-dose,and high-dose groups(2.08,4.16,and 8.32 mL·kg-1),and a positive control group(butylphthalein soft capsules at 6.25 mg·kg-1),with 10 rats in each group.Each group was given water or drug intragastrically,once a day,for consecutive 7 days.The neurological function scores was observed on the 1st,3rd,and 7th day after the modeling.After 7 days of administration,the pathological changes in rats cerebral ischemic tissue were observed,and the percentage of cerebral infarction volume was measured.The serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-8 levels and TNF-α,IL-1β,IL-8 mRNA expression,and NF-κB inhibitory protein α(p-IκBα),nuclear transcription factor-κBp65(NF-κBp65),phosphorylated nuclear transcription factors-κBp65(p-NF-κBp65)protein expression in the ischemic brain tissue were also detected.Results Compared with the sham operation group,the Longa score of the model group significantly increased after 7 days of administration,and a distinct pale infarct lesion appeared in the right brain(P＜0.01).TNF-α,IL-1β,IL-8 and TNF-α,IL-1β,IL-8 mRNA expressions were significantly increased(P＜0.01),while the protein expressions of p-IκBα,NF-κBp65 and p-NF-κBp65 were significantly upregulated(P＜0.05 or P＜0.01).HE staining showed a loose network structure in the ischemic tissue area of the brain,with disordered cells,structural defects,and even atrophy and deformation,reduced quantity,nuclear pyknosis and fragmentation.Compared with the model group,after 7 days of administration,the Longa scores of rats in each dose groups on the 7th day of intervention were significantly decreased,and other detection indicators were also decreased(P＜0.05 or P＜0.01).Conclusion Pinggan Huoxue mixture can greatly improve the levels of inflammatory factors in CIRI and alleviate brain injury,whose mechanism is related to the regulation of the NF-κB signaling pathway.
NETL
NSTL
万方数据
