滋阴明目丸对视网膜色素变性模型小鼠自噬的影响OA

Objective To investigate the mechanism of Ziyin Mingmu Pills(滋阴明目丸,ZMP)in treatment of retinitis pigmentosa.Methods Forty-eight rd 10 mice were randomly divided into four groups,a model group,a Leding group,a low-dose and a high-dose ZMP group,with 12 mice in each group.Twelve C57BL/6 mice served as blank control group.The low-dose ZMP group was administered with 4.5 g/(kg·d)of ZMP solution by gavage,while the high-dose ZMP group received 9 g/(kg·d)of ZMP solution,and the Leding group received 0.15 g/(kg·d)of Leding soft capsule solution by gavage,once daily for 28 consecutive days.After the intervention,retinal morphology was assessed using optical coherence tomography and fundus photography.Transmission electron microscopy was used to observe autophagy in retinal tissue.Western Blot was used to detect the expression of mammalian target of rapamycin(mTOR),phosphoinositide 3-kinase(PI3K),Beclinl,autophagy-related protein 5(ATG5),and microtubule-associated protein 1 light chain 3(LC3)proteins in retinal tissues.Real-time fluorescence quantitative PCR was employed to measure the mRNA expression of mTOR,PI3K,Beclin1,ATG5,and LC3 in retinal tissues.Results Compared with the blank control group,the model group showed disordered retinal structure,unclear layering,and thinner retinal thickness(P＜0.01).The fundus appeared bluish-grey with uneven color distribution and extensive pigmentation.Retinal mitochondrial structures were damaged,and autophagic vesicles were visible.The protein and mRNA expression levels of mTOR and PI3K decreased,while those of Beclin1,ATG5,and LC3Ⅱ/LC3Ⅰ increased(P＜0.01).Compared with the model group,the Leding group and the low-dose and high-dose ZMP groups showed varying degrees of improvement in retinal morphology and fundus condition,along with increased retinal thickness(P＜0.01).Mitochondrial damage was reduced,and the number of autophagosomes decreased.In the low-dose and high-dose ZMP groups,the protein and mRNA expression levels of mTOR and PI3K increased,while those of Beclin1,ATG5 and LC3Ⅱ/LC3Ⅰ decreased(P＜0.05 or P＜0.01).Conclusion ZMP can improve tretinal tissue morphology and structure in retinitis pigmentosa model mice by inhibiting autophagy,thereby delaying the progression of retinal degeneration and protecting vision function.