Mechanism analysis of fisetin regulating LKB1-AMPK-mTOR-p70S6K pathway to improve oligonasthenospermia in rats
- VernacularTitle:非瑟酮调节LKB1-AMPK-mTOR-p70S6K通路改善大鼠少弱精子症
- Author:
Li-Bang CHEN
1
;
Bing-Xiang SHEN
;
Chun-Yuan HE
;
Wei-Chen ZHAO
;
Wei CHANG
;
Tong-Sheng WANG
Author Information
- Keywords: fisetin; oligasthenospermia; AMPK; mTOR; p70S6K; LKB1
- From: Chinese Pharmacological Bulletin 2024;40(7):1296-1301
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the protective effect of fisetin on testis and sperm of rats with oligoasthenosper-mia and to explore its mechanism.Methods The rat model of oligoasthenospermia was established.The rats were randomly divided into the blank group,model group,low-,medium-,and high-dose fisetin treat-ment groups,and LKB1 agonist group,with 10 rats in each group.ELISA was used to detect the levels of FSH,LH,T,E2 and PRL.Flow cytometry was used to detect sperm cell apoptosis.HE staining was used to detect testicular tissue damage.Transmission electron microscopy was used to detect the ultrastructure of sperm cells.qRT-PCR and Western blot were used to detect the mRNA and protein expression of LKB1,AMPK,mTOR,and p70S6K.Results Compared with the blank group,the levels of FSH,LH,PRL,T and other hormones in the model group and LKB1 ago-nist group were significantly reduced,and sperm cell apoptosis and testicular injury were severe.The ex-pressions of LKB1 and p-AMPK/AMPK were signifi-cantly up-regulated,while the expressions of mTOR and p-p70S6K/p70S6K were significantly down-regula-ted(P＜0.05).Compared with the model group,af-ter different doses of fisetin treatment,the number of apoptotic sperm cells was significantly reduced,the levels of FSH,LH,PRL,T and other hormones markedly increased,the expression of LKB1 and p-AMPK/AMPK was significantly down-regulated,and the expression of mTOR and p-p70S6K/p70S6K was evidently up-regulated(P＜0.05).Conclusion Fi-setin is effective in the treatment of oligoasthenospermia rats,which may be related to LKB1-AMPK-mTOR-p70S6K signaling pathway.
