Experimental Study On Improving Premature Ovarian Failure Rats Induced By Cisplatin By Zuogui Pills Based On PI3K/AKT/mTOR

Objective:This study was conducted to investigate the mechanism of Zuogui pills in improving cisplatin-induced premature ovarian failure model rats with cisplatin-induced premature ovarian failure by PI3K/AKT/m TOR signaling pathway.Methods:Screening of 60 female sd rats of grade SPF normal cycle,Weight（200±20）g,at 8weeks Randomly selected 8 blank groups,All the remaining rats were involved in modeling,Collectively known as modeling groups.During the first and eighth days,rats were injected intraperitoneally with cisplatin injection at 6 mg/kg,To establish an animal model of premature ovarian failure,After modeling,The rats were randomly divided into model group,Zuogui pills group,Bujiale（estradiol valerate）group,Zuogui pills joint Bujiale low dose group and Zuogui pills joint Bujia high dose group.Vaginal exfoliative cell smear was taken continuously during modeling.The next day after the mold,continuous gavage for 4 weeks.After the treatment,The contents of serum estradiol（E₂）,follicle stimulating hormone（FSH）,luteinizing hormone（LH）,progesterone（P）and testosterone（T）were measured by enzyme linked immunosorbent assay,Detection of p-PI3K,p-AKT,p-m TOR protein expression in ovarian tissue by western blotting,And the changes of ovarian tissue structure were observed by hematoxylin-eosin staining.All data are analyzed by spss 19.0 software.Results:（1）General situation:compared with the blank group,the rats in the model group had obvious weight loss,mental retardation,less movement,dim hair color and so on.After the drug intervention,compared with the model group,the weight of the rats in each drug intervention group was obviously increased.（2）Organ coefficient of rats:compared with the blank group,the ovarian coefficient and uterine coefficient of the model group decreased significantly（P<0.01）,and the ovarian coefficient and uterine coefficient of the Zuogui pills group increased to a certain extent compared with the model group（P<0.05）.（3）Serum sex hormones in rats:compared with the blank group,the serum FSH,LH content in the model group was significantly higher than that in the blank group（P<0.01）,and the serum E₂content was significantly lower than that in the blank group（P<0.01）.And the effect of Bujiale group and Zuogui pills joint Bujiale low dose group was the same（P>0.05）.（4）p-PI3K,p-AKT,p-m TOR protein:compared with the blank group,the p-PI3K,p-AKT,p-m TOR expression in the model group was decreased and the difference was statistically significant（P<0.01）.The p-PI3K,p-AKT,p-m TOR expression content of each drug treatment group increased in varying degrees,compared with the model group（P<0.01）.Conclusion:（1）The combination of Zuogui pills and Bujiale is superior to single drug.（2）Zuogui pills can up-regulate the expression of ovarian p-PI3K,p-AKT,p-m TOR protein,which may promote follicle development and maturation and improve the ovarian function of cisplatin injury by regulating PI3K/AKT/m TOR signaling pathway to inhibit autophagy of rat granulosa cells.