小续命汤调控PINK1/Parkin介导的线粒体自噬改善脑缺血再灌注损伤大鼠的神经功能OA

Objective:To investigate the neuroprotective effects of Minor Xuming Decoction on cerebral ischemia-reperfusion injury(CI-RI)and its underlying mechanisms.Methods:A total of 60 healthy male SPF-grade SD rats were randomly divided into four groups:sham-operated group,model group,Minor Xuming Decoction low-dose group(15 g·kg-1)and Minor Xuming Decoction high-dose group(30 g·kg-1).Except the sham-operated group,rats in all groups were established focal cerebral ischemia-reperfusion injury models using the modified Zea-Longa method.After model establishment,rats in each group were given intragastric administration of cor-responding drugs once daily for 7 consecutive days;rats in the sham-operated and model groups received an equal volume of normal sa-line instead.The Zea-Longa neurological deficit scale was adopted to score neurological dysfunction.The Morris water maze test was per-formed to evaluate cognitive function.TTC staining was used to calculate cerebral infarct volume.Transmission electron microscopy(TEM)was applied to observe mitochondrial ultrastructure.Mitochondria were isolated to detect adenosine triphosphate(ATP)content.Western blotting was utilized to measure the protein expression levels of LC3,Parkin,p62 and Beclin-1.Results:Compared with the sham-operated group,the model group showed remarkably higher neurological deficit scores and larger cerebral infarct volumes.In the Morris water maze test,rats in the model group presented prolonged escape latency,fewer platform crossings,and shorter residence time in the target quadrant.For cortical tissue protein detection,the LC3-Ⅱ/LC3-Ⅰ ratio,as well as the expression levels of Beclin-1,Parkin and p62,were significantly upregulated.In addition,mitochondrial number and ATP content were markedly reduced.All above differ-ences were statistically significant(P<0.05).Compared with the model group,the Minor Xuming Decoction high-dose group exhibited significantly lower neurological deficit scores and smaller cerebral infarct volumes.Meanwhile,the rats presented shortened escape laten-cy,increased number of platform crossings,prolonged residence time in the target quadrant,and markedly elevated swimming speed.In addition,the LC3-Ⅱ/LC3-Ⅰ ratio and the expression levels of Beclin-1,Parkin and p62 were significantly downregulated,while mito-chondrial number and ATP content were remarkably increased.All differences above were statistically significant(P<0.05).Conclu-sion:Minor Xuming Decoction exerts neuroprotective effects against CIRI.Its underlying mechanism may be associated with inhibiting excessive activation of the PINK1/Parkin pathway,modulating mitophagy,and preserving the structural and functional integrity of mito-chondria.