The Effect of Ziyin Mingmu Formula(滋阴明目方)on Retinal Tissue Apoptosis and Endoplasmic Reticulum Stress in Retinitis Pigmentosa Model Mice
Objective To study the effect of Ziyin Mingmu Formula(滋 阴 明目方)on retinitis pigmentosa mice and its possible mechanism.Methods Sixty rd10 mice were randomly divided into model group,vitamin A group,and Ziyin Mingmu Formula low-,medium-,and high-dose groups,12 mice in each group;twelve C57BL/6 mice as the blank group.The mice in Ziyin Mingmu Formula low-,medium-,and high-dose groups were given 13.5,27.0 and 54.0 g/(kg·d)of Ziyin Mingmu Formula by gavage,respectively;mice in the Vitamin A group were given 750 IU/(kg·d)of vitamin A soft capsule by gavage;mice in the blank group and model group were given 13.5 ml/(kg·d)of physiological saline by gavage.Each group was gavaged once a day for 28 days.Fundus photography and optical coherence tomography were used to detect the morphology of the fundus and retina,TUNEL method was used to detect apoptosis,microtitre digital PCR and immunofluorescence double staining were used to detect glucose-regulated pro-tein 78(GRP78),inositol-requiring enzyme 1(IRE1),activated transcription factor 6(ATF6),and C/EBP homolo-gous protein(CHOP)mRNA and protein expression levels.Results In the model group,optic discs were yellowish,fundus was atrophic with large pigmentation.The retinal blood vessels were thinned,a large number of vascular white sheaths were seen,the retinal cell nuclei disorganised,and a large number of apoptotic cells were seen;the fundus conditions of the mice in all dosages of Ziyin Mingmu Formula and the vitamin A group were improved to varying degrees compared with those of the model group,the apoptotic cells reduced,with Ziyin Mingmu Formula middle-and high-dose groups showing more significant improvement.Compared with the blank group,the retinal thickness of mice in the model group reduced,and the expression of GRP78,IRE1,ATF6,CHOP mRNA and protein elevated(P＜0.01).Compared with the model group,retinal thickness increased and GRP78,IRE1,ATF6 mRNA and pro-tein expression decreased in the vitamin A group and Ziyin Mingmu Formula medium-and high-dose groups;CHOP mRNA and protein expression decreased in low-,medium-,and high-dose groups of Ziyin Mingmu Formula(P＜0.05 or P＜0.01).Compared with vitamin A group and the low-dose group of Ziyin Mingmu Formula,retinal thick-ness increased in the high-dose group of Ziyin Mingmu Formula(P＜0.01).Compared with vitamin A group,GRP78,ATF6,IRE1,and CHOP mRNA expression decreased in the medium-and high-dose groups of Ziyin Mingmu Formula,and GRP78 and CHOP protein expression decreased(P＜0.05 or P＜0.01).Compared with the low-dose group of Ziyin Mingmu Formula,CHOP protein expression reduced in the medium-and high-dose groups of Ziyin Mingmu Formula(P＜0.01).Conclusion Ziyin Mingmu Formula can reduce apoptosis of retinal tissues by inhibiting the endoplasmic reticulum stress response,thus slowing down the progression of retinopathy and protecting visual function in a dose-dependent manner.
万方数据
维普
