基于"脾肾双补"理论的金精丸通过6-甲基腺嘌呤甲基化修饰治疗脾肾两虚型少弱精症机制研究OA

Objective Based on the traditional Chinese medicine theory of"dual tonification of the spleen and kidney",to investigate the mechanism by which Jinjing Pills improves oligoasthenozoospermia due to spleen-kidney deficiency by regulating N6-methyladenosine(m6A)methylation modification.Methods A total of 105 patients with oligoasthenozoospermia due to spleen-kidney deficiency who were treated in the Department of Urology of Kunshan Hospital of Traditional Chinese Medicine from May 2020 to June 2023 were selected.After propensity score matching(PSM)at a 1∶1 ratio,they were assigned to a treatment group and a control group,with 45 patients in each group.The control group received levocarnitine oral solution and lifestyle intervention,while the treatment group received Jinjing Pills in addition to the treatment given to the control group.Both groups were treated for 3 months.Semen parameters(semen volume,sperm concentration,etc.),m6A modification levels in sperm RNA,and clinical efficacy were compared between the two groups.The association between semen parameters and m6A modification levels was analyzed using a multiple linear regression model.Dynamic changes in semen parameters between groups were analyzed using a generalized estimating equation(GEE)model.Results At 1 and 3 months of treatment,semen volume,sperm concentration,progressive motility(PR)rate,sperm viability,straight-line velocity,and normal morphology rate were all significantly higher in both groups than before treatment(P<0.05),and were higher in the treatment group than in the control group at the corresponding time points(P<0.05).At 1 and 3 months of treatment,m6A levels in both groups were significantly lower than before treatment(P<0.05),and were lower in the treatment group than in the control group at the corresponding time points(P<0.05).Repeated-measures analysis of variance showed significant time effects,group effects,and interaction effects for m6A levels in both groups(P<0.05).Multiple linear regression showed that m6A levels were negatively correlated with semen volume(β=-0.274),sperm concentration(β=-0.434),PR rate(β=-0.356),sperm viability(β=-0.432),straight-line velocity(β=-0.576),and normal morphology rate(β=-0.272)(P<0.05).GEE analysis showed a time-dependent cumulative advantage in sperm quality improvement in the treatment group(P<0.001).The total effective rates were 88.89%(40/45)in the treatment group and 68.89%(31/45)in the control group,with a significantly higher total effective rate in the treatment group(P<0.05).Conclusion Jinjing Pills can significantly improve sperm quality in patients with oligoasthenozoospermia due to spleen-kidney deficiency,and its mechanism may be associated with inhibition of abnormal N6-methyladenosine methylation modification in sperm RNA.