PT - JOURNAL ARTICLE AU - Bingrui Zhao AU - Zhe Wang AU - Xinyue Liang AU - Xiaoyan Wang AU - Kai Lin AU - Lihua Yuan AU - Jing Jiang AU - Cong Xu AU - Daolai Zhang AU - Yeying Sun AU - Weihua Bian TI - Inhibition of the postsynaptic density protein 95 on the protective effect of Ang-(1-7)–Mas on cerebral ischaemia injury AID - 10.1136/svn-2021-001396 DP - 2022 Jun 20 TA - Stroke and Vascular Neurology PG - svn-2021-001396 4099 - http://svn.bmj.com/content/early/2022/06/20/svn-2021-001396.short 4100 - http://svn.bmj.com/content/early/2022/06/20/svn-2021-001396.full AB - Background Postsynaptic density protein-95 (PSD95) plays an important role in cerebral ischaemia injury, but its mechanism needs further research. This study aimed to explore the role of PSD95 in (Ang-(1-7))-Mas-mediated cerebral ischaemia protection and its regulatory mechanism.Methods Oxygen–glucose deprivation (OGD) neuron and rat middle cerebral artery occlusion (MCAO) models were used as in vitro and in vivo models, respectively. TAT-MAS9C was used to disrupt the interaction between PSD95 and Mas. The recombinant PSD95 adenovirus (Ad-PSD95) was used to overexpress PSD95 in neurons.Results Results showed that in OGD neurons, Ang-(1-7) could promote cell viability; reduce cell apoptosis; reduce the cell membrane localisation of Mas; upregulate the expression levels of pAKT, bcl-2 and I-κB; and downregulate the expression levels of Bax, pI-κB, tumour necrosis factor alpha and interleukin-1β. TAT-MAS9C could enhance the aforementioned effects of Ang-(1-7). However, the PSD95 overexpression inhibited the aforementioned effects of Ang-(1-7). In the MCAO rat model, the 2,3,5-triphenyltetrazolium chloride (TTC) staining showed that Ang-(1-7) reduced the infarct volume. The Morris water maze test showed that the number of crossings over the platform area in the Ang-(1-7) group was significantly increased. TAT-MAS9C could promote the protective effect of Ang-(1-7).Conclusions Results suggested that PSD95 alleviated the activation of AKT and the inhibition of nuclear factor kappa B signalling pathway mediated by the Ang-(1-7)–Mas complex, thereby reducing neuronal activity, increasing apoptosis and inhibiting the Ang-(1-7)–Mas-mediated cerebral ischaemia protection.Data are available upon reasonable request. The raw data will be made available by the authors upon reasonable request.