Combination of tetrandrine and 3-n-butylphthalide protects against cerebral ischemia-reperfusion injury via ATF2/TLR4 pathway

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.

Keywords:

• Cerebral infarction
• cell apoptosis
• tetrandrine
• 3-n-butylphthalide
• ATF2/TLR4 signaling

Acknowledgments

This study is funded by Hebei Provincial Medical Science Research Key Project Program (20170976).

Disclosure statement

The authors declared no competing interests.

Data availability statement

All data generated or analyzed during the present study were included in this article.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.