Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):667-673
doi:10.19378/j.issn.1003-9783.2024.05.008
The Effect of Buyang Huanwu Decoction on Cerebral Ischemia-Reperfusion Injury in Rats by Regulating Lipid Metabolism via cAMP/PKA/PPAR γ Pathway
Yin OUYANG 1 ; Bowei CHEN ; Yingfei LIU ; Fanzuo ZENG ; Jian YI ; Fengming TIAN ; Baiyan LIU
Affiliations
Keywords
Buyang Huanwu Decoction; cerebral ischemia reperfusion; cAMP/PKA/PPARγ signaling pathway; lipid metabolism; neuroprotection; rats
Country
China
Language
Chinese
Abstract
Objective To explore the mechanism of Buyang Huanwu Decoction against cerebral ischemia-reperfusion injury in rats by regulating lipid metabolism through the cAMP/PKA/PPARγ pathway.Methods 60 rats were randomly divided into sham operation group(Sham),model group(Model),Buyang Huanwu Decoction low-dose group(BHD-L),Buyang Huanwu Decoction medium-dose group(BHD-M),Buyang Huanwu Decoction high-dose group(BHD-H)and Butylphthalide group(NBP).The cerebral ischemia-reperfusion model was prepared by transient middle cerebral artery embolization.The BHD low-,medium-and high-groups were given different doses of Buyang Huanwu Decoction(6.413,12.825,25.65 g·kg-1)by intragastric administration.The NBP group was administered with Butylphthalide(54 mg·kg-1).The sham operation group and the model group were administered with an equal volume of distilled water,all given for 14 days.The rats were subjected to neurobehavioral scoring.HE staining was used to observe brain pathological changes,and the kit was used to detect the levels of phosphocholine(PC),phosphatidylethanolamine(PE),diacylglycerol(DAG),and free fatty acid(FFA)on the ischemic side.RT-qPCR and Western Blot were applied to detect the mRNA and protein expressions of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),and peroxisome proliferator-activated receptor γ(PPARγ).Results Compared with the sham group,the neurological deficit score was significantly increased(P<0.01),pathomorphological damage in ischemic cortex was found,the contents of PC and PE were reduced,the contents of DAG and FFA were increased(P<0.01),and cAMP mRNA expression increased(P<0.05)in the model group.Compared with the model group,the neurological deficit score of the BHD-L group was decreased(P<0.05),and the neurological deficit score of the BHD-M,BHD-H and NBP groups was significantly decreased(P<0.01),the cells in each treatment group were regularly arranged,the intercellular spaces were reduced,and the normal cells were increased.PC and PE were significantly increased,DAG and FFA were significantly decreased(P<0.01)in the BHD-M,BHD-H and NBP groups.PC was increased,FFA and DAG were decreased in the BHD-L group(P<0.05,P<0.01).The mRNA level of PPARγ was increased in the BHD-L group(P<0.05),and the mRNA and protein levels of cAMP,PKA,and PPARγ were increased in the other treatment groups(P<0.05,P<0.01).Conclusion Buyang Huanwu Decoction has a neuroprotective effect on cerebral ischemia-reperfusion injury rats,and its mechanism may be related to regulating the expression of key factors in the cAMP/PKA/PPARγ signaling pathway and lipid metabolism.
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