地黄饮子改善脑缺血再灌注损伤的作用及机制研究OA

Objective:To explore the therapeutic effect of Dihuang Yinzi decoction on cerebral ischemia-reperfusion injury(CIRI)and its underlying molecular mechanism.Methods:A rat model of cerebral ischemia-reperfusion injury(CIRI)was established.30 SD rats were randomly divided into five groups,with 6 rats per group:sham operation group,model group,low-dose Dihuang Yinzi group(6 g/kg),high-dose Dihuang Yinzi group(12 g/kg),and positive control group(nimodipine,10 mg/kg).All rats were administered intragastrically once a day for 28 consecutive days.Modified neurological severity scores(mNSS)were used to assess neurological dysfunction in rats.Hematoxylin-eosin(HE)staining was applied to observe the pathological changes of brain tissue.The levels of TNF-α,IL-6,IL-1β,MDA,SOD and GSH-PX in brain tissue were detected by ELISA.Transmission electron microscopy(TEM)and Western blot were adopted to observe the morphological changes of autophagosomes and mitochondria in brain tissue,as well as the protein expressions of LC3II/LC3I,Beclin1,Fis1 and Drp1.Results:Compared with the model group,both low-and high-dose Dihuang Yinzi groups and the nimodipine group significantly decreased the mNSS scores and alleviated cerebral pathological damage in rats.Meanwhile,the levels of proinflammatory factors(TNF-α,IL-6,IL-1β)and oxidative stress indicator MDA were markedly reduced,while the activities of antioxidant enzymes SOD and GSH-PX were notably elevated.In addition,Dihuang Yinzi and nimodipine treatment reduced the number of autophagosomes,increased the number of mitochondria,and downregulated the protein expression levels of LC3II/LC3I,Beclin1,Fis1 and Drp1 in brain tissue.Conclusion:Dihuang Yinzi decoction exerts a protective effect against cerebral ischemia-reperfusion injury,which may be closely related to the inhibition of mitochondrial fission and excessive autophagy.