Abstract
The present study explored the modulating apoptosis effect of hydrogen sulfide (H2S) in subarachnoid hemorrhage (SAH) rats and its exact mechanism. A rat SAH model established by intravascular puncturing was used for the present study. After giving NaHS (donor of H2S), an L-type calcium channel opener (Bay K8644), or a calcium channel agonist (nifedipine), the neurological function of the rats, associated pathological changes, and expression of apoptosis-related proteins (Bcl-2, Bax, and caspase-3) and microtubule-associated protein (MAP-2) were examined. The concentration of H2S and expression of cystathionine beta synthase in the hippocampus changed upon early brain injury (EBI) after SAH. Compared with the SAH group, the neurological function of the rats and microstructure observed by electron microscopy were better in the SAH + NaHS group and SAH + Bay K8644 group. It was observed that apoptosis was more obvious in the SAH group than in the control group and was alleviated in the SAH + NaHS group. Furthermore, the alleviating effect of NaHS was partially weakened by nifedipine, indicating that the effect of anti-apoptosis in H2S might be correlated with the calcium channel. The expression of Bax and caspase-3 was elevated, while the expression of Bcl-2 decreased in the SAH group but improved in the SAH + NaHS and SAH + Bay K8644 group. Compared with the SAH + NaHS group, the expression of pro-apoptotic proteins was higher in the SAH + NaHS + nifedipine group. Therefore, upon EBI following SAH, the H2S system plays an important neurological protective effect by modulating the function of the L-type calcium channel and inhibiting apoptosis.
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This work was supported by Chinese National Nature Science Foundation (Grant No. 81541119), Youth Clinical Research Project of Peking University First Hospital (2019CR02), and Peking University First Hospital Cross Clinical Study Foundation.
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HZD and CWW were responsible for the study design and manuscript writing. SLS and JYZ were responsible for the study execution and data collection. LL was responsible for data management, data analysis, and interpretation. All the authors read and approved the final manuscript.
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All animals were treated in compliance with the National Research Council’s Guide for the Care and Use of Laboratory Animals (1996). The study was approved by the Institutional Review Board of the Ethics Committee of Affiliated Hospital of Peking University First Hospital. This article does not contain any studies with human participants performed by any of the authors.
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Duan, HZ., Wu, CW., Shen, SL. et al. Neuroprotective Effects of Early Brain Injury after Subarachnoid Hemorrhage in Rats by Calcium Channel Mediating Hydrogen Sulfide. Cell Mol Neurobiol 41, 1707–1714 (2021). https://doi.org/10.1007/s10571-020-00940-0
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DOI: https://doi.org/10.1007/s10571-020-00940-0