Zhang Huiyu, Guo Minfang, Yu Jingwen, Li Yanhua, Zhao Yijing, Zhang Jing, Chai Zhi, Yu Jiezhong, Ma Cungen
Institute of Brain Science, Shanxi Datong University, Datong 037009, China.
Institute of Brain Science, Shanxi Datong University, Datong 037009; Shanxi University of Chinese Medicine, Taiyuan 030619, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2018 Jun;34(6):505-510.
Objective To evaluate the influence of Fasudil on the lipopolysaccharide (LPS)-induced activation and inflammatory response of astrocytes and TLR4/ NF-κB signaling pathway. Methods Astrocytes were separated from the cerebral cortex of newly-born C57BL/6 mice and cultured in vitro. The cells were divided into PBS control group, 1 μg/mL LPS stimulation group, 1 μg/mL LPS combined with 15 μg/mL Fasudil treatment group. The production of NO in the cell supernatant was detected by Griess reagent. The levels of tumor necrosis factor-α (TNF-α), interleukin -6(IL-6), IL-10 and IL-4 were measured by ELISA. The expressions of glial fibrillary acidic protein (GFAP) and TLR4 in the astrocytes were detected by immunofluorescence cytochemistry. The protein levels of GFAP, TLR4 and p-NF-κBp65 were assessed by Western blot analysis. Results Compared with the PBS control group, the levels of NO, TNF-α and IL-6 in the LPS group significantly increased, but the levels of IL-10 and IL-4 decreased. Fasudil treatment significantly inhibited LPS-induced the secretion of NO, TNF-α and IL-6 and enhanced the production of IL-10 and IL-4. The expression of GFAP significantly decreased in the Fasudil treatment group, and the protein levels of TLR4 and p-NF-κBp65 also decreased. Conclusion Fasudil can inhibit LPS-induced astrocyte activation and inflammatory response by blocking TLR4/NF-κB signaling pathway.
