Exploring the Protective Mechanism of Zhenlong Xingnao Capsule on Cerebral Ischemia-reperfusion Injury in Rats based on PGC-1α Pathway
Objective:To explore the protective mechanism of Zhenlong Xingnao Capsule on cerebral ischemia-rep-erfusion injury in rats based on the peroxisome proliferator-activated receptor-y coactivator-1 α(PGC-1 α)pathway.Methods:SD rats were randomly divided into sham operation group(Sham),model group(I/R),Zhenlong Xingnao low,medium and high dose groups(ZLXN1,ZLXNm,ZLXNh).There were 12 rats in each group.Except for Sham,the modi-fied Longa method was used to replicate the rat model of ischemic brain injury.After modeling,except for I/R,the three groups of rats were given Zhenlong Xingnao 50,100 and 200 mg/(kg·d)by gavage,and the I/R group and Sham group were given 0.9％sodium chloride solution simultaneously.The treatment course was 1 week.Neurological deficit scores were performed at 6,12,and 24 hours after modeling.After one week of treatment,ELISA was used to detect the levels of superoxide dismutase(SOD),malondialdehyde,glutathione peroxidase,tumor necrosis factor-α,and interleukin-6 in hippocampal tissue,and Western blot was used to detect the mRNA expressions of nuclear transcription factor κ B(NF-κ B),PGC-1 α,nuclear respiratory factor-1(NRF1),and mitochondrial transcription factor A(TFAM).Results:Compared with the I/R group,the neurological deficit scores of the ZLXNm and ZLXNh groups at each time point were significantly reduced,and the differences were statistically significant(P＜0.05);the levels of interleukin-6,tumor ne-crosis factor-α,and malondialdehyde in the Zhenlong Xingnao Capsule groups were significantly reduced,while the levels of glutathione peroxidase were significantly increased,and the differences were statistically significant(P＜0.05).There was no significant difference in SOD activity between the ZLXN1 group and the I/R group(P＞0.05),while SOD in the ZLXNm and ZLXNh groups increased significantly(P＜0.05).The expression of PGC-1 α and TFAM mRNA in the hippocampus of each dose group of Zhenlong Xingnao was significantly increased(P＜0.05),the expression of NF-κ B protein was significantly decreased in the ZLXNm and ZLXNh groups(P＜0.05),and the expression of NRF1 pro-tein was significantly increased in the ZLXNm and ZLXNh groups(P＜0.05).Conclusion:Zhenlong Xingnao Capsule can promote the recovery of neurological function in rats with cerebral ischemia-reperfusion injury,and inhibit oxidative stress and inflammatory response to play a neuroprotective role.Its mechanism may be related to the downregulation of NF-κ B expression and the activation of PGC-1 α signaling pathway.
Zhenlong XingnaoCerebral ischemia-reperfusion injuryOxidative stressPGC-1 αNF-κ B
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