Author(s)

Miao Huo¹, Qian Zhang², Ziyu Zhao¹, Ruifen Xu¹, Xingxing Zheng¹, Guang Yang¹, Jiao Guo^1*

¹Department of Anesthesiology, Shaanxi Provincial People’s Hospital, Xi’an, China.
²Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an, China.

Purpose: This research evaluates the efficacy of astaxanthin (AX) on cerebral ischemia/reperfusion (I/R) injury in rats and elucidates the potential mechanism of its neuronal protective effect. Methods: Rats were subjected to a middle cerebral artery occlusion/reperfusion (MCAO/R) model. Fifty grown male Sprague-Dawley (SD) rats were divided into 5 groups, including sham operation group (Sham), MCAO/R group, MCAO/R+AX group, MCAO/R+ AX+ Scramble group and MCAO/R+AX+ si-PPAR-γ group. The neurological score and cerebral infarction volume were evaluated after surgery. Rat microglia (RM) were stimulated by lipopolysaccharide (LPS) to form an inflammatory environment. LPS-induced RM cells were incubated with different concentrations of AX (1, 5 or 10 μg/mL), then cell viability, the expression of microglial activation markers, including cytokines (IL-1β, IL-6 and TNF-α), cluster of differentiation 68 (CD68), inducible nitric oxide synthase (iNOS) and CD206 and the expression of PPAR-γ and phosphorylated P65 (p-P65) proteins were determined. Cells were treated with pcDNA-PPAR-γ, as well as treatment with si-PPAR-γ or PPAR-γ antagonist GW9662 before AX treatment, and then cell activation mediators were tested. Results: AX inhibits LPS-induced RM cells activation and enhanced the expression level of PPAR-γ protein in way of dose-dependent, and pcDNA-PPAR-γ treatment had the same effect as AX. While si-PPAR-γ transfection or PPAR-γ suppressant GW9662 treatment reversed the effect of AX, and cut down the level of PPAR-γ protein and augmented the level of p-P65 protein. In addition, AX treatment alleviated the infarct volume, and sensorimotor and cognitive functions of MCAO/R model rats. Conclusion: AX alleviates LPS-induced microglial injury and has a protective effect on rat cerebral I/R injury by regulating the PPAR-γ/NF-κB pathway.

Astaxanthin, Cerebral Ischemia/Reperfusion Injury, RM Cells, PPAR-γ, P65

Huo, M. , Zhang, Q. , Zhao, Z. , Xu, R. , Zheng, X. , Yang, G. and Guo, J. (2022) Astaxanthin Regulates PPAR-γ/NF-κB Pathway to Mitigate Nerve Injury after Cerebral Ischemia/Reperfusion in Rats. Journal of Biosciences and Medicines, 10, 294-310. doi: 10.4236/jbm.2022.109021.