黄芪甲苷调节小胶质细胞活化减轻脑缺血再灌注大鼠神经炎症损伤的研究OA

Objective:To explore the effects of astragaloside Ⅳ(AS-Ⅳ),an active component of Astragalus membranaceus,on cerebral ischemia-reperfusion injury(CIRI)in rats via regulating the activation of brain microglia.Methods:SD rats were randomly divided into sham operation group,model group,AS-Ⅳ group(20 mg/kg)and nimodipine group(0.7 mg/kg).Except for the sham operation group,rats in the other groups were established with CIRI models.The corresponding drugs were intraperitoneally injected immediately after reperfusion in the administration groups,twice a day for 3 consecutive days.At 72 hours after reperfusion,Zea Longa scoring method was used to evaluate the neurological function,TTC staining to test cerebral infarct volume,HE staining to observe the pathological changes of brain tissues,immunofluorescence staining to detect the number of ionized calcium binding adaptor molecule 1(Iba1)and cluster of differentiation 68(CD68)positive cells in brain tissues,ELISA to determine the levels of TNF-α,IL-1β and IL-6 in brain tissues,and Western blot to detect the protein expressions of NF-κB p65 and p-NF-κB p65,and the ratio of p-NF-κB p65 to NF-κB p65 was calculated.Results:Compared with the sham operation group,the model group showed neurological deficits,large cerebral infarcts and neuronal damage.The numbers of Iba1+,CD68+and Iba1+CD68+cells were significantly increased(P<0.05).TNF-α,IL-1β and IL-6,as well as the ratio of p-NF-κB p65 to NF-κB p65 were elevated(P<0.05).Compared with the model group,both the AS-Ⅳ group and the nimodipine group showed decreased neurological function scores(P<0.05),reduced cerebral infarct volume(P<0.05)and alleviated neuronal injury.The counts of Iba1+,CD68+and Iba1+CD68+cells were declined(P<0.05),and the contents of TNF-α,IL-1β,IL-6 and the p-NF-κB p65/NF-κB p65 ratio were also decreased(P<0.05).Conclusion:By regulating cerebral microglial activation and inhibiting the NF-κB pathway to reduce the production and release of pro-inflammatory factors TNF-α,IL-1β and IL-6,AS-Ⅳ relieves neuroinflammatory injury,ameliorates neurological function and brain histopathological lesions,and ultimately plays a protective role in CIRI rats.