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| Effect of Pristimerin on Cognitive Function and Neuroinflammation in Ischemic Stroke Rats by Regulating the cGAS/STING Signaling Pathway |
| LIN Xiaoyan, FANG Lixin, HUANG Lixia, et al |
| Qingdao Central Hospital Affiliated to Qingdao University, Shandong Qingdao 266013, China |
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Abstract Objective: To investigate the effects of pristimerin (PT) on cognitive function and neuroinflammation in ischemic stroke rats by modulating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS/STING) signaling pathway. Methods: The middle cerebral artery occlusion (MCAO) model was established by using the filament occlusion method.Rats were randomly assigned to the control group,MCAO group,low,medium,and high-dose PT groups (PT-L group,PT-M group,PT-H group),and PT-H+DMXAA group (PT-H+DMXAA group).Zea-Longa score was employed to evaluate the neurological behavior of rats.The Morris water maze was used to assess the cognitive ability of the rats.Cerebral infarction area was calculated by using the 2,3,5-chlorophenyltetrazolium (TTC) staining method.Pathological changes in rat brain tissue were observed via hematoxylin and eosin (HE) staining.Enzyme-linked immunosorbent assay (ELISA) was performed to measure serum levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β).Western blot analysis was utilized to determine the expression levels of M1 marker (iNOS),M2 marker (Arg-1),cGAS,and STING proteins in microglia of rat brain tissue. Results: When compared to the control group,rats in the MCAO group exhibited significantly increased neurological deficit scores,prolonged escape latencies,larger cerebral infarction areas,elevated IL-6 and IL-1β levels,and higher expression of iNOS,cGAS,and STING.The expression of Arg-1 decreased significantly (P<0.05).In comparison to the MCAO group,rats in the PT groups showed significantly reduced neurological deficit scores,escape latencies,cerebral infarction areas,IL-6 and IL-1β levels,as well as the expression of iNOS,cGAS,and STING.The expression of Arg-1 increased significantly (P<0.05) in a dose-dependent manner.In comparison to the PT-H group,rats in the PT-H+DMXAA group had significantly higher neurological deficit scores,prolonged escape latencies,larger cerebral infarction areas,increased IL-6 and IL-1β levels,and higher expression of iNOS,cGAS,and STING.The expression of Arg-1 decreased significantly (P<0.05). Conclusion: Pristimerin can mitigate cognitive impairment and neuroinflammatory damage in ischemic stroke rats.Its mechanism of action may be associated with the inhibition of the cGAS/STING signaling pathway.
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2023, Vol. 29 
