Cunfang Li1, Aijun Chai1, Yongchao Gao1, Xuan Qi1, Xuguang Zheng2. 1. Department of Pharmacy, Shijiazhuang People's Hospital, Shijiazhuang, China. 2. Department of Pharmacy, The First Hospital of Hebei Medical University, Shijiazhuang, China.
Abstract
OBJECTIVE: Cerebral infarction (CI) is the mayor reason of death in China. Reperfusion is the only immediate treatment for acute cerebral infarction. However, blood reperfusion recovery may cause ischemia-reperfusion (I/R) injuries. The purpose of this study was to investigate the effects of Tetrandrine (TTD) and 3-n-Butylphthalide (NBP) on cerebral I/R injury. MATERIALS AND METHODS: I/R was used to establish CI model in vivo. TTD was performed to analyze cerebral infarction volume. OGD was applied to establish CI model in vitro. Flow cytometry and TUNEL assays were utilized to determine the cell death. ELISA was conducted to determine the release of cytokines. mRNA and protein expressions were detected using qRT-PCR and western blot. RESULTS: We found that NBP + TTD treatment significantly reduced cerebral infarction volume and inhibited the death of neurons in vivo. Moreover, NBP + TTD treatment suppressed the apoptosis and inflammatory response of neurons in vitro. Additionally, NBP + TTD suppressed the expression of activator transcription factor 2 (ATF2). However, overexpression of ATF2 contributed to the degeneration of neurons. Moreover, ATF2 transcriptionally activated Toll-like receptor 4 (TLR4). NBP + TTD inactivated ATF2/TLR4 signaling. CONCLUSIONS: Taken together, TTD combined with NBP protected against cerebral infarction by inhibiting the inflammatory response and neuronal cell apoptosis via inactivating ATF2/TLR4 signaling pathways. This may provide an alternative for I/R injury.
OBJECTIVE: Cerebral infarction (CI) is the mayor reason of death in China. Reperfusion is the only immediate treatment for acute cerebral infarction. However, blood reperfusion recovery may cause ischemia-reperfusion (I/R) injuries. The purpose of this study was to investigate the effects of Tetrandrine (TTD) and 3-n-Butylphthalide (NBP) on cerebral I/R injury. MATERIALS AND METHODS: I/R was used to establish CI model in vivo. TTD was performed to analyze cerebral infarction volume. OGD was applied to establish CI model in vitro. Flow cytometry and TUNEL assays were utilized to determine the cell death. ELISA was conducted to determine the release of cytokines. mRNA and protein expressions were detected using qRT-PCR and western blot. RESULTS: We found that NBP + TTD treatment significantly reduced cerebral infarction volume and inhibited the death of neurons in vivo. Moreover, NBP + TTD treatment suppressed the apoptosis and inflammatory response of neurons in vitro. Additionally, NBP + TTD suppressed the expression of activator transcription factor 2 (ATF2). However, overexpression of ATF2 contributed to the degeneration of neurons. Moreover, ATF2 transcriptionally activated Toll-like receptor 4 (TLR4). NBP + TTD inactivated ATF2/TLR4 signaling. CONCLUSIONS: Taken together, TTD combined with NBP protected against cerebral infarction by inhibiting the inflammatory response and neuronal cell apoptosis via inactivating ATF2/TLR4 signaling pathways. This may provide an alternative for I/R injury.