Effects of Ziyin Mingmu Formula on PERK-ATF4 signaling pathway in rd10 mice with retinitis pigmentosa
Objective To study the effects and the possible mechanisms of Ziyin Mingmu Formula(ZYMMF)on mice with retinitis pigmentosa(RP).Methods Sixty rd 10 mice were randomized into model group(equal volume of saline),Vitamin A(VitA)group[VitA 750 IU/(kg·d)],and low-,medium-,and high-dose ZYMMF groups[ZYMMF decoction 13.5,27,54 g/(kg·d)].Twelve C57BL/6 mice were used as the blank group(equal volume of saline).All groups were administered by gavage for 28 days.HE staining was used to observe the pathological changes in retinal tissue,TUNEL assay was used to check the apoptosis in retinal tissue,and droplet digital PCR and immunofluorescence double staining were used to examine the mRNA and protein expressions of protein kinase RNA-like endoplasmic reticulum kinase(PERK)and activating transcription factor 4(ATF4)in retinal tissue.Results Compared with the blank group,the model group showed significant retinal atrophy and thinning,with the retinal pigment epithelial(RPE)cells being invisible,the outer nuclear layer disappearing,and a decrease in retinal thickness(P＜0.01),along with a significant reduction in the number of retinal cells and the presence of a large number of apoptotic cells;the mRNA and protein expression levels of PERK and ATF4 increased(P＜0.01).Compared with the model group,the VitA group and each dose group of ZYMMF showed improvement in retinal condition and increased thickness(P＜0.01);the number of cells increased and the number of apoptotic cells decreased;the mRNA expression levels of PERK and ATF4 decreased(P＜0.01).Compared with the model group,the protein expression levels of PERK and ATF4 in the VitA group and the medium-and high-dose ZYMMF groups decreased(P＜0.01);the protein expression level of ATF4 in the low-dose ZYMMF group was reduced(P＜0.01).Compared with the low-dose ZYMMF group,the high-dose ZYMMF group showed an increase in retinal thickness(P＜0.05),and the medium-and high-dose ZYMMF groups showed a decrease in protein expression of ATF4 and mRNA expression of PERK(P＜0.01).Compared with the VitA group,the high-dose ZYMMF group showed a decrease in protein expression of ATF4(P＜0.05),and the medium-and high-dose ZYMMF groups exhibited a decrease in mRNA expression of PERK(P＜0.01).Conclusion ZYMMF can improve the morphology of mouse retina and reduce the apoptosis of retinal tissue,and its molecular mechanism may be related to the regulation of PERK-ATF4 signaling pathway.
万方数据
维普
