Mechanism Research Of Icariin Improves Chemotherapy-induced Premature Ovarian Failure In Rats By Inhibiting Oxidative Stress

Objetive:By administering icariin to rats with chemotherapy-induced premature ovarian failure,the therapeutic effect of icariin on rats with chemotherapy-induced ovarian failure was confirmed.The general condition,body weight change,ovarian wet weight,ovarian index,and detection were observed.Serum hormone indicators,detection of oxidative stress and apoptosis related indicators and related signal pathway upstream and downstream protein indicators,to explore the effect of icariin on oxidative stress-induced apoptosis and improve the premature ovarian failure of chemotherapy.Method:1.To observe the role of icariin in the chemotherapy-induced POF model in rats: After intraperitoneal injection of CP to establish a rat model of chemotherapy-induced POF in rats,icariin was administered to establish icariin to interfere with chemotherapy-induced POF model(ICA+CP group).In addition,icariin was administered alone as a positive control(ICA group),and the control group(Control group)was used as a reference.To observe the changes of mental activity,eating,hair growth and other general conditions of icariin administration in rats,and compare the effects of icariin on body weight,ovarian wet weight and ovarian index in rats.The effect of saponin on ovarian pathology and the number of follicles in ovarian sections were counted.The effect of icariin on ovarian tissue apoptosis was observed.The serum AMH hormone levels in each group were detected.2.To investigate the mechanism of icariin inhibiting oxidative stress in protecting oxidative premature ovarian failure in rats: a control group was used as a reference to detect the expression of oxidative stress and apoptosis-related protein Bax/Bcl-2/SOD1/SOD2 in ovarian tissues of each group was detected,as well as PI3K/Akt/mTOR signaling pathway-related proteins PI3K-P110?,PI3K-P85,p-Akt.(ser473),p-mTOR,T-Akt,T-mTOR expression,observe the mechanism of icariin to improve the premature ovarian failure of chemotherapy in rats.Results:1.Therapeutic effect of icariin on chemotherapy-induced POF rats: At the beginning of the experiment,there was no difference in body weight between the groups(P>0.05).At the end of the experiment,compared with the Control group,the body weight of the rats in the CP group was significantly lower(P<0.01),and there was no significant difference in the body weight between the ICA group and the ICA+CP group(P>0.05).Compared with CP group,the body weight of rats in ICA group and ICA+CP group were significantly increased(P<0.01).Compared with the Control group,the ovarian wet weight of the rats in the CP group was significantly decreased(P<0.01),the wet weight of the ovaries in the ICA group was significantly increased(P<0.05),and the wet weight of the ovaries in the ICA+CP group was not significantly changed(P>0.05);Compared with CP group,the ovarian wet weight of ICA group and ICA+CP group were significantly increased(P<0.01).Compared with the Control group,the number of primordial follicles in the rats in the CP group and the ICA+CP group was significantly lower(P<0.01),the number of primordial follicles in the ICA+CP group was higher than that in the CP group,and the number of primordial follicles in the ICA group was significantly higher(P<0.05).The number of growing follicles and the number of mature follicles: Compared with the Control group,the number of follicles and the number of mature follicles in the rats in the CP group and the ICA+CP group were significantly lower(P<0.01).There was no significant difference in the number of follicles and the number of mature follicles in the ICA group(P>0.05).Compared with CP group,the number of follicles and mature follicles in ICA group and ICA+CP group increased significantly(P<0.01),but the number of follicles and mature follicles in ICA+CP group were lower than those in ICA group.Total follicles: Compared with the Control group,the total number of follicles in the CP group and the ICA+CP group was significantly lower(P<0.01),and there was no significant difference in the total follicles in the ICA group(P>0.05);compared with CP group,the total number of follicles in ICA group and ICA+CP group increased significantly(P<0.01),but the total number of follicles in ICA+CP group was lower than that in ICA group.Compared with the Control group,the apoptosis of the CP group was significantly increased(P<0.01),and there was no significant difference in the ICA group.Compared with the CP group,the apoptosis of the ICA+CP group was significantly reduced(P<0.01).Compared with the Control group,the serum AMH level in the CP group was significantly lower(P<0.01),and the serum AMH level in the ICA group was increased,but not significant(P>0.05).Compared with CP group,serum AMH was significantly increased in ICA+CP group,and the difference between the two groups was statistically significant(P<0.01).The sera of the ICA group were slightly higher than the Control group,but significantly higher than the ICA+CP group and the CP group.2.The effect of icariin on the expression of Bax/Bcl-2/SOD1/SOD2 protein and PI3K/Akt/mTOR signaling pathway-related proteins in ovarian tissue of rats with chemotherapy-induced POF: Compared with the Control group,the protein expression of Bcl-2,SOD1 and SOD2 in the CP group was significantly decreased(P<0.01);the expression of Bax protein was significantly increased(P<0.01).Compared with CP group,the protein expression of Bcl-2,SOD1 and SOD2 in ICA+CP group was significantly increased(Bcl-2: P<0.01;SOD1: P<0.05;SOD2: P<0.01);Bax protein expression was significantly reduced(Bax: P < 0.01).Compared with the Control group,the protein expression of PI3K-P110?,PI3K-P85,p-Akt(ser473)and p-mTOR in the CP group was significantly decreased(P<0.01);and there was no significant change in the protein expression of T-Akt and T-mTOR(P>0.05).Compared with CP group,the protein expression of PI3K-P110?,PI3K-P85,p-Akt(ser473)and p-mTOR in ICA+CP group was significantly increased(PI3K-P110?: P<0.01;PI3K-P85: P<0.05;p-Akt(ser473): P<0.01;p-mTOR(ser2448): P<0.01);there was no significant change in protein expression of T-Akt and T-mTOR(P>0.05).Conclusion:1.Intraperitoneal injection of cisplatin can induce ovarian injury in rats,leading to premature ovarian failure;2.Rats with chemotherapy-induced premature ovarian failure may lead to increased levels of oxidative stress and aggravate apoptosis of ovarian cells;3.Icariin can reduce the oxidative stress level of rats with oxidative premature ovarian failure,reduce the apoptosis of rat ovarian cells,and thus treat premature ovarian failure;4.Icariin may activate PI3K/Akt/mTOR signaling pathway through phosphorylation to inhibit oxidative stress-induced ovarian cell apoptosis and improve the premature ovarian failure of chemotherapy in rats.