Protective effect of cryptotanshinone on premature ovarian insufficiency rats by regulating the SDF-1/CXCR4 axis
OBJECTIVE To investigate the protective effect of cryptotanshinone on premature ovarian insufficiency(POI)rats and its potential mechanism based on stromal cell-derived factor-1(SDF-1)/CXC subfamily receptor 4(CXCR4)axis.METHODS POI rat model was established by intraperitoneal injection of vinylcyclohexene(VCD).The successfully modeled rats were randomly divided into model group,cryptotanshinone low-dose group(50 mg/kg),cryptotanshinone high-dose group(100 mg/kg),and cryptotanshinone high-dose+AMD3100 group(100 mg/kg cryptotanshinone+2.5 mg/kg CXCR4 inhibitor AMD3100),with 10 rats in each group.Another 10 rats were injected with normal saline instead of VCD as the control group.Rats in each drug group were given intragastrical or(and)intraperitoneal injection of the corresponding drug once a day for 4 weeks.The levels of estradiol(E2),luteinizing hormone(LH)and follicle-stimulating hormone(FSH)in serum and reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in ovarian tissue were detected in each group.The morphology of ovarian tissue was observed.The cell apoptosis of ovarian tissue,as well as the mRNA expressions of SDF-1,CXCR4 and the protein expressions of caspase-3,B cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),SDF-1,CXCR4 were detected.RESULTS Compared with the control group,the ovarian atrophied,the number of primitive follicles decreased,the number of atretic follicles increased,and the damage was obvious in the model group.Serum E2 level,SOD and GSH-Px levels in ovarian tissue,the mRNA expressions of SDF-1 and CXCR4,and the protein expressions of Bcl-2,SDF-1 and CXCR4 in ovarian tissue were all significantly decreased or down-regulated;the levels of FSH and LH in serum,ROS and MDA levels in ovarian tissue,the cell apoptosis rate,and the protein expressions of caspase-3 and Bax in ovarian tissue were increased or upregulated significantly(P＜0.05).Compared with model group,the ovarian tissue lesions of rats in cryptotanshinone low-dose and high-dose groups were significantly improved,and each quantitative index was significantly improved(P＜0.05).AMD3100 could significantly reverse the improvement effect of cryptotanshinone on the above indexes(P＜0.05).CONCLUSIONS Cryptotanshinone can reduce ovarian cell apoptosis and oxidative stress in POI rats by activating the SDF-1/CXCR4 axis,regulating serum hormone levels,thereby improving ovarian injury.
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