黄芪甲苷对神经炎症的改善作用及机制研究OA

OBJECTIVE To investigate the improvement effects and mechanism of astragaloside Ⅳ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced neuroinflammation.METHODS BV2 cells were divided into control group,LPS group,AS-Ⅳgroups at concentrations of 20 and 40 μmol/L,and dexamethasone group(2 μmol/L).Except for control group,neuroinflammation model was established with LPS(1 μg/mL)in other groups after medication.The levels of inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nitric oxide(NO)]in cell supernatant were measured in each group.Mice were randomly divided into normal group,model group,positive control group(Aspirin enteric-coated tablet,20 mg/kg),AS-Ⅳ low-and high-dose groups(10,20 mg/kg),with 6 mice in each group.Mice in each group were administered the corresponding drug/normal saline via gavage/intraperitoneal injection,once a day,for 14 consecutive days.Except for normal group,other groups were intraperitoneally injected with LPS(250 μg/kg)1 hour after daily administration of the drug/normal saline to establish neuroinflammation model.Serum levels of IL-6 and TNF-α were measured 2 h after the last medication;histopathological morphology of cerebral tissue in mice were observed;the co-localization of inducible nitric oxide synthase(iNOS)/ionized calcium binding adapter molecule 1(Iba1)and CD206/Iba1 in the cerebral cortex region of mice was observed;the expressions of proteins related to the nuclear factor-κB(NF-κB)/mitogen-activated protein kinase(MAPK)signaling pathway in brain tissue of mice were also determined,including NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),p38 MAPK,phosphorylated p38 MAPK(p-p38 MAPK),extracellular signal-regulated kinase(ERK),and phosphorylated ERK(p-ERK).RESULTS In the cell experiments,compared with control group,the levels of IL-6,TNF-α and NO in the cell supernatant of the LPS group were increased significantly(P＜0.05);compared with LPS group,the levels of IL-6,TNF-α and NO were decreased significantly in the administration groups(P＜0.05).In the animal experiments,compared with the normal group,the serum levels of IL-6 and TNF-α,the number of iNOS/Iba1 co-localization positive cells in the cerebral cortex,and the phosphorylation levels of p38 MAPK,NF-κB p65 and ERK proteins in brain tissue were all significantly increased/elevated in model group(P＜0.05);the number of CD206/Iba1 co-localization positive cells in the cerebral cortex region significantly decreased(P＜0.05).The neurons in the cerebral cortex and the CA3 region of the hippocampus displayed a disordered arrangement.Compared with model group,above quantitative indexes of mice were all reversed significantly in administration groups(P＜0.05);the neuronal cells in the cerebral cortex and the CA3 region of the hippocampus exhibited a relatively orderly arrangement.CONCLUSIONS AS-Ⅳ may inhibit the activation of the NF-κB/MAPK signaling pathway,promote the M2-type polarization of microglia,and thereby suppress neuroinflammatory responses.