| Objective1.Systematic review of the efficacy and safety of Chinese medicine for invigoratin g the kidney and relieving liver in the treatment of diminished ovarian reserve,and pr oviding evidence-based evidence for the treatment of DOR by Chinese medicine.2.To investigate the effect of Jiajian Guishen Pill(JGP),a type of herb formula,on level of ovarian histomorphology,serum hormone levels and the signaling pathwa y of phosphatidyl inositol 3-kinase(PI3K)/protein kinase(AKT)/mammalian target of rapamycin(mTOR)in ovarian tissue of the mice with diminished ovarian reserve.Method1.The computer searched the China Knowledge Network,Wanfang,Weipu,PubMe d,Cochrane Library databases,and the search time was the establishment of the datab ase-December 1,2019,collected randomized controlled trials of tonifying kidney and r elieving liver and traditional Chinese medicine for DOR.The main outcome indicators:AMH,FSH,AFC;secondary outcome indicators:LH,E2,total effectiveness,TCM sy mptom score,OVA,incidence of adverse reactions,literature selection Data extraction are based on inclusion and exclusion criteria,and quality assessment is using the "bias risk assessment tool",and then using RevMan5.3 software do the Meta-analysis of out come indicators2.Ninety ICR female mice were randomly divided into six groups including cont rol group,model group,western medicine group,JGP low-,medium-,and high-dose g roups,each with 15 rats.The animal model of diminished ovarian reserve was establis hed by ip.4-vinylcyclohexene diepoxide(VCD).The three JGP groups were orally ad ministrated the corresponding drugs for 30 days while the control group and model gr oup were administrated saline solution.On the 31st day,blood was collected.HE stai ning was used to observe the morphological variations of ovarian tissue.The levels of AMH,FSH,LH and E2 were detected by immunoassay.The expression of PI3K,A KT and mTOR in mouse ovarian tissue was detected by Western Blot.The expression of PI3K,AKT,and mTOR mRNA in mouse ovarian tissue was detected by SYBR Green I Real Time PCR.Results1.A total of 20 literatures were included in this study,with a total of 1399 patien ts.The meta-analysis showed that the levels of AMH,AFC,and E2 levels and clinica 1 effectiveness of the test group were higher than those in the control group and the levels of FSH,LH,TCM symptom scores and incidence of adverse drug reactions of the test group was lower than the control group,in which the difference was statistica lly significant,but there was no significant difference in OVA;it indicated that the C hinese medicine for tonifying kidney and relieving liver can improve ovarian function,and according to sub-group analysis of it,compared with the western medicine,the tr aditional Chinese medicine for tonifying kidney and relieving liver was more effective in total effectiveness.and the incidence of adverse reactions was lower in the experi mental group than in the control group,but in AMH,AFC,E2,FSH,and TCM symp tom scores are equally effective;the Chinese medicine combined with western medicin e is higher in AMH,AFC,E2,OVA and the clinical effectiveness,and is lower in FS H,LH,TCM symptom score,compared with the western medicine alone.compared wit h blank group,the Chinese medicine is higher in AMH,AFC,lower in the FSH and TCM symptom scores,and equivalent in E2.2.In animal experiments:The results of HE staining showed that in the blank co ntrol group,the number of follicles in the ovarian tissue of was abundant,and the outl ines of the primordial follicle,preantral follicle,and antral follicle were clearly visible,and there were a large number of corpus luteum distribution.In the model group,the number of follicles was significantly decreased,meantime the atretie follicle increased,and the number of corpus luteum was scarce;the number of follicles in the western medicine group was relatively abundant,and more corpus luteum and a few atretie fol licle and primordial follicle were seen.In the JGP high-dose groups,Follicles at all lev els can be seen,with a large number of corpus luteum,and a small number of atretic follicles can be seen,followed by the medium-dose group.The low-dose group is main ly dominated by atretic follicles,a rare and irregular corpus luteum.Compared with the blank control group,FSH and LH in the model group were significantly higher(p<0.01),and AMH and E2 were significantly lower(p<0.01);Compared with the model gro up,FSH and LH were significantly lower in the JGP medium-and high-dose and wes tern groups(p<0.01 or p<0.05),AMH was significantly higher(p<0.01),and E2 was sig nificantly higher in the JGP high-dose and western groups(p<0.01);Compared with the western medicine group,in the JGP medium-,and low-dose group,AMH and E2 was sig nificantly lower(p<0.01 or p<0.05),FSH was higher(p<0.05),and in the JGP low-dos e group,LH was significantly higher(p<0.01);Compared with the low-dose group,in t he JGP medium-dose group,the AMH was significantly higher(p<0.01)and the FSH was lower(p<0.05),and in in the JGP high-dose group,the FSH and LH was decreased(p<0.01 or p<0.05).and E2 was significantly increased(p<0.01);Compared with the middle-dose group,AMH and E2 in the JGP high-dose were significantly higher(p<0.01).SYBR Green I Real Time PCR show that compared with the blank control group,the PI3K,AKT,and mTOR mRNA expression levels in the the model group were sig nificantly lower(P<0.01);Compared with the model group,the PI3K,AKT,and mTOR mRNA expression levels in the JGP high-dose group were significantly higher(P<0.01),and the levels of AKT and mTOR mRNA in the low-and medium-dose group w ere significantly higher(P<0.01).Compared with the western medicine group,the PI3 K,AKT,and mTOR mRNA expression levels in the JGP low-and medium-dose grou p were significantly lower(P<0.01),the PI3Kand mTOR mRNA expression levels in th e JGP high-dose group significantly were lower(P<0.05 or P<0.01),with the AKT mR NA expression levels in the JGP high-dose group significantly higher(P<0.01).Compare d with the JGP of low-dose group,the PI3K,AKT,and mTOR mRNA expression leve ls in the JGP high-dose group was higher(P<0.01)and the AKT,and mTOR mRNA expression levels in the JGP medium-dose group was higher(P<0.05 or P<0.01).Compa red with the JGP of the medium-dose group,the PI3K of the JGP high-dose group w as higher(P<0.05),the PI3K,AKT and mTOR mRNA expression levels in the JGP high-dose group was higher(P<0.01).Western Blot show that the PI3K,AKT and mT OR of the model group was lower than those of the moder group(P<0.05 or P<0.01);The PI3K and AKT of the JGP medium-,and high-dose groups and western medicine group were higher than those of the model group(P<0.01).The mTOR level of the JGP high dose group and western medicine group was higher than that of the model group,but the difference was not statistically significant(P>0.05).Compared with the western medicine group,the PI3K,AKT of the JGP low-dose group was lower(P<0.01)and the PI3K of the JGP medium-dose group was lower(P<0.05).Compared with t he JGP of low-dose group,the PI3K of the JGP medium-dose group was higher(P<0.01)and the PI3K and AKT of the JGP high-dose group was higher(P<0.05 or P<0.01).Compared with the JGP of the medium-dose group,the PI3K of the JGP high-dose group was higher(P<0.05).Conclusion1.Chinese medicine for tonifying the kidney and relieving liver has a certain effe ct in treating diminished ovarian reserve,and has fewer adverse reactions occur than western medicine,which is more safety.However,due to the low quality of the inclu ded methodological literature,a multi-center,large sample and high-quality test is still needed.2.JGP can increase all kinds of follicle,reduce follicular atresia and improve ser um hormone levels.besides,it may improve ovarian function in DOR mice induced by VCD by increasing the expression of PI3K,AKT and mTOR mRNA and proteins. |
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