孕酮对Aβ所致星形胶质细胞炎症小体表达的影响及机制研究

The protective mechanism of progesterone on Aβ-induced inflammasomes activation in astrocytes

目的研究神经甾体孕酮对Aβ所诱导星形胶质细胞NLRP3炎症小体表达的调节作用及潜在的分子机制。方法正常培养新生鼠原代脑皮质星形胶质细胞,分别应用ELISA、免疫荧光、Western blot等试验方法检测孕酮对于星形胶质细胞IL-1β分泌水平,以及pro-IL-1β和NLRP3炎症小体表达的影响,并研究调节星形胶质细胞NLRP3表达活化与内质网应激的可能关系。结果与Aβ干预组相比,孕酮处理能够显著性抑制Aβ所致星形胶质细胞IL-1β、pro-IL-1β合成分泌,并能够显著降低炎症小体NLRP3表达。另外,应用内质网应激诱导剂处理星形胶质细胞发现,其能明显促进星形胶质细胞IL-1β、pro-IL-1β合成分泌。与之相反,内质网应激抑制剂能够明显阻断孕酮对于Aβ所致NL-RP3表达的抑制作用。结论孕酮能够通过调节星形胶质细胞内质网应激水平,显著抑制Aβ所致炎症小体NLRP3表达活化。

Aim To investigate the possible regulatory effect of neurosteroid progesterone on Aβ-induced NL-RP3 inflammasomes activation in astrocytes and the po-tential molecular mechanism.Methods The astro-cytes of cerebral cortex of newborn SD rat pups were enrich-cultured,and the level of IL-1βin supernatant and pro-IL-1β,NLRP3 expression in lysates of astro-cytes following progesterone treatment were detected by ELISA,immunofluorescence and Western blot.The possible relationship was investigated between NLRP3 expression and ER stress activation in astrocytes follow-ing progesterone treatment.Results Compared with Aβ-treated group,progesterone significantly inhibited the synthesis and secretion of IL-1β,pro-IL-1βand NLRP3 expression in Aβ-induced astrocytes.In addi-tion,ER stress inducer significantly increased the syn-thesis and secretion of IL-1βand pro-IL-1βin astro-cytes.Contrarily,ER stress inhibitor significantly in-hibited the neuroprotection of progesterone in regulating Aβ-induced NLRP3 expression.Conclusion Proges-terone significantly inhibits Aβ-induced NLRP3 expres-sion by regulating ER stress activation in astrocytes.