The Mechanism of Astragaloside IV in NOD-like Receptor Family Pyrin Domain Containing 3 Inflammasome-mediated Pyroptosis after Intracerebral Hemorrhage


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Abstract

Background::Intracerebral hemorrhage (ICH) is one of the most common subtypes of stroke.

Objectives::This study aimed to investigate the mechanism of Astragaloside IV (AS-IV) on inflammatory injury after ICH.

Methods::The ICH model was established by the injection of collagenase and treated with ASIV (20 mg/kg or 40 mg/kg). The neurological function, water content of the bilateral cerebral hemisphere and cerebellum, and pathological changes in brain tissue were assessed. The levels of interleukin-1 beta (IL-1β), IL-18, tumor necrosis factor-alpha, interferon-gamma, and IL-10 were detected by enzyme-linked immunosorbent assay. The levels of Kruppel-like factor 2 (KLF2), NOD-like receptor family pyrin domain containing 3 (NLRP3), GSDMD-N, and cleaved-caspase-1 were detected by reverse transcription-quantitative polymerase chain reaction and Western blot assay. The binding relationship between KLF2 and NLRP3 was verified by chromatin-immunoprecipitation and dual-luciferase assays. KLF2 inhibition or NLRP3 overexpression was achieved in mice to observe pathological changes.

Results::The decreased neurological function, increased water content, severe pathological damage, and inflammatory response were observed in mice after ICH, with increased levels of NLRP3/GSDMD-N/cleaved-caspase-1/IL-1β/IL-18 and poorly-expressed KLF2 in brain tissue. After AS-IV treatment, the neurological dysfunction, high brain water content, inflammatory response, and pyroptosis were alleviated, while KLF2 expression was increased. KLF2 bonded to the NLRP3 promoter region and inhibited its transcription. Down-regulation of KLF2 or upregulation of NLRP3 reversed the effect of AS-IV on inhibiting pyroptosis and reducing inflammatory injury in mice after ICH.

Conclusion::AS-IV inhibited NLRP3-mediated pyroptosis by promoting KLF2 expression and alleviated inflammatory injury in mice after ICH.

About the authors

Honggang Wu

Department of Neurosurgery, West China Hospital, Sichuan University

Email: info@benthamscience.net

Shu Chen

Department of Cerebrovascular Disease, The People's Hospital of Leshan

Email: info@benthamscience.net

Guoliang You

Department of Cerebrovascular Disease, The People's Hospital of Leshan

Email: info@benthamscience.net

Bo Lei

Department of Cerebrovascular Disease, The People's Hospital of Leshan

Email: info@benthamscience.net

Li Chen

Department of Cerebrovascular Disease, The People's Hospital of Leshan

Email: info@benthamscience.net

Jiachuan Wu

Department of Cerebrovascular Disease, The People's Hospital of Leshan

Email: info@benthamscience.net

Niandong Zheng

Department of Cerebrovascular Disease, The People's Hospital of Leshan

Email: info@benthamscience.net

Chao You

Department of Neurosurgery, West China Hospital, Sichuan University

Author for correspondence.
Email: info@benthamscience.net

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