[Effect of PR-957 on the formation of A1 reactive astrocytes]
Objective: To investigate the effect of PR-957 on the formation of A1 reactive astrocytes.
Methods: Primary astrocytes were cultured from the cerebral cortices of 1-day-old female rats. The cells were divided into three groups: control, lipopolysaccharide (LPS), and LPS+PR-957. The LPS group was treated with LPS at a concentration of 5 μmol/L for 48 hours. The LPS+PR-957 group was first treated with PR-957 (200 nmol/L) for 1 hour, followed by LPS treatment for 48 hours. The expression of complement 3 (C3, a marker of A1 reactive astrocytes) and tumor necrosis factor alpha (TNF-α) was measured using enzyme-linked immunosorbent assay (ELISA). Quantitative real-time PCR was used to assess the mRNA expression levels of glypican-6 (GPC6), SPARC-like 1 (SPARCL1), and lipocalin-2 (LCN2). All experiments were repeated three times independently.
Results: C3 expression was negligible in the control group but was observed in both the LPS and LPS+PR-957 groups, with significantly lower C3 expression in the LPS+PR-957 group (P<0.05). The expression pattern of TNF-α mirrored that of C3. Compared to the control group, both the LPS and LPS+PR-957 groups exhibited significantly reduced mRNA expression levels of GPC6 and SPARCL1, but significantly increased mRNA expression of LCN2 (P<0.001). When compared to the LPS group, the LPS+PR-957 group showed significantly higher mRNA levels of GPC6 and SPARCL1, and significantly lower mRNA levels of LCN2 (P<0.001). Conclusions: LPS induces the transformation of astrocytes into A1 reactive astrocytes, and PR-957 effectively inhibits the formation of LPS-induced A1 reactive astrocytes.