Abstract： Objective To observe the effect of Bushen Ningxin Decoction(补肾宁心汤,BSNXD)on rats with premature ovari-an insufficiency(POI)and explore its mechanism.Methods The 21-day-old rats were randomly divided into control group,mod-el group,BSNXD low,medium and high dose groups.The control group was given intraperitoneal injection of sesame oil,and the other groups were given intraperitoneal injection of 4-vinylcyclohexene diepoxide(VCD)solution for 15 days.And then the treat-ment groups were given low,medium and high dose of BSNXD respectively.The control group and the model group were given the same volume of normal saline.Forty-five days later,the rats were sacrificed for sampling.Then,high-throughput sequencing technology combined with public database mining was used to explore the changes of miRNA and mRNA expression profiles and predict the target genes and potential functions of microRNA-144.Results As time went on,the estrous cycle of rats in the model group was gradually becoming disorganized,which was manifested as shortening of estrous period and prolongation of estrous inter-val.The improvement was found after BSNXD treatment.HE staining of ovary showed that the follicular and luteal counts of the model group were significantly reduced.After BSNXD intervention,the follicular and luteal counts were significantly increased,es-pecially in the medium and high dose groups.HE staining of uterus showed the endometrium of the model group was thinned and the number of uterine glands in the tube wall was significantly reduced.After BSNXD intervention,the endometrium was thickened and the number of glands was significantly increased.The results of public database analysis suggested that microRNA 144 was sig-nificantly down-regulated in POI rats,which was consistent with the results of high-throughput sequencing.Meanwhile,the ex-pressions of Beclin-1,LC3 Ⅰ and ULK1 were significantly up-regulated in POI rats.MiRNA target gene prediction and function-al enrichment analysis showed that microRNA144 interacted with Beclin-1,LC3 Ⅰ and ULK1 and microRNA144 target genes were significantly enriched in autophagy and AKT/mTOR pathways.PCR results showed that microRNA-144 expression signifi-cantly decreased in the model group,and significantly increased after BSNXD treatment.Western blot results showed that the ex-pressions of AKT/mTOR pathway and autophagy pathway-related proteins,including Beclin-1,LC3 Ⅰ and ULK1 in the model group were inhibited and promoted,respectively.After BSNXD treatment,the expression of AKT/mTOR protein was significantly increased,while the expression of autophagy related proteins was significantly decreased.Conclusion BSNXD can protect the ovar-ian reserve function of rats with premature ovarian insufficiency and improve the endocrine state of rats and slow down follicular atresia.The mechanism may be related to the up-regulation of microRNA 144/AKT/mTOR pathway to inhibit excessive autophagy.