丹皮酚通过调节p38丝裂原活化蛋白激酶对缺血性脑卒中大鼠神经炎症的影响OACSTPCD
Influence of Paeonol on neuroinflammation in ischemic stroke rats by regulating p38 mitogen-activated protein kinase signaling pathway
目的 探讨丹皮酚对缺血性脑卒中大鼠神经炎症的影响及其机制.方法 使用SPF级雄性SD大鼠构建缺血性脑卒中大鼠模型,将大鼠分为假手术组(Sham组)、模型组(Model组)、丹皮酚组(Paeonol组,20 mg/kg丹皮酚)、丹皮酚联合p38丝裂原活化蛋白激酶(p38 MAPK)激活剂组(Paeonol+Anisomycin组,20 mg/kg丹皮酚+2 mg/kg Anisomycin).造模 48 h后观察大鼠神经功能缺损评分,检测脑梗死体积,使用TUNEL染色及免疫荧光染色观察神经元凋亡及小胶质细胞激活情况,酶联免疫吸附测定法检测缺血半暗带区脑组织肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β和IL-6 水平,Western blot检测p-p38 MAPK、p38 MAPK蛋白表达.结果 与Sham组比较,Model组大鼠神经功能损伤严重,脑组织出现白色梗死灶,神经功能缺损评分及脑梗死体积、神经元凋亡率、小胶质细胞数量及TNF-α、IL-1β和IL-6水平、p-p38 MAPK蛋白表达水平升高,差异均有统计学意义(P<0.05);与Model组比较,Paeonol组大鼠神经功能缺损评分及脑梗死体积、神经元凋亡率、小胶质细胞数量及TNF-α、IL-1β和IL-6水平、p-p38 MAPK表达水平降低,差异均有统计学意义(P<0.05);与Paeonol组比较,Paeonol+Anisomycin组大鼠神经功能缺损评分及脑梗死体积增加,且丹皮酚改善缺血性脑卒中大鼠脑损伤及炎症反应的作用可被Anisomycin逆转(P<0.05).结论 丹皮酚可能通过抑制p38 MAPK通路,抑制小胶质细胞激活及炎症反应,减轻缺血性脑卒中引起的脑损伤.
Objective To investigate the influence of Paeonol on neuroinflammation in ischemic stroke rats and its mechanism.Methods Male SD rats with SPF level were used to establish a rat model of ischemic stroke.Rats were devided into Sham group,Model group,Paeonol group(20 mg/kg Paeonol),and Paeonol combined with p38 mitogen-activated protein kinase(p38 MAPK)activator group(Paeonol+Anisomycin group,20 mg/kg Paeonol+2 mg/kg Anisomycin).After modeling for 48 hours,neurological function deficit score were observed,cerebral infarction volume was detected,neuronal apoptosis and microglia activation were assessed by TUNEL staining and immunofluorescence staining.The levels of tumor necrosis factor α(TNF-α),interleukin(IL)-1β and IL-6 in the brain tissue of the ischemic penumbra were detected by enzyme linked immunosorbent assay(ELISA).The expression of p-p38 MAPK and p38 MAPK was measured by Western blot.Results Compared to the Sham group,rats in the Model group had severe neurological damage,white infarct lesions in the brain tissue,increased neurological function deficit score,cerebral infarct volume,neuron apoptosis rate,microglia cell count and levels of TNF-α,IL-1β,IL-6,and p-p38 MAPK protein expression,the differences were statistically significant(all P<0.05).Compared to the Model group,rats in the Paeonol group exhibited reduced neurological function deficit score,cerebral infarct volume,neuron apoptosis rate,microglia cell count and levels of TNF-α,IL-1β and IL-6,and p-p38 MAPK protein expression,the differences were statistically significant(P<0.05).Compared to the Paeonol group,rats in the Paeonol+Anisomycin group showed increased neurological function deficit score and cerebral infarct volume,and the protective effect of Paeonol on ischemic stroke-induced brain injury and inflammatory response could be reversed by Anisomycin(P<0.05).Conclusion Paeonol may alleviate ischemic stroke-induced brain injury by inhibiting the p38 MAPK pathway,suppressing microglia activation and inflammatory response.
周华勇;赵玉萍;杨旭;张珊珊;季一飞
637000 四川省南充市中心医院(川北学院第二临床学院)神经内科
丹皮酚缺血性脑卒中神经炎症p38丝裂原活化蛋白激酶信号通路
PaeonolIschemic strokeNeuroinflammationP38 mitogen-activated protein kinase signaling pathway
《心脑血管病防治》 2024 (002)
16-20,封3 / 6
四川省南充市科技局科研项目(NSMC20170454)
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