探讨“阳化气、阴成形”理论的聚精汤通过抗氧化应激改善精子线粒体结构和功能治疗弱畸形精子症的临床研究

Treatment of asthenoteratozoospermia with Jujing Decoction by improving the structure and function of sperm mitochondria via antioxidant stress based on the theory of“Yang-Qi transformation and Yin morphologization”

目的:与抗氧化应激药联合精子能量代谢剂对比观察聚精汤治疗弱畸形精子症的临床疗效和作用机制。方法:采用随机对照临床研究,按纳入标准将弱畸形精子症患者分为聚精汤治疗组(聚精汤口服)和阳性对照组(天然型维生素E软胶囊联合左卡尼汀口服液)。分别观察治疗前和治疗12周后患者精液常规参数、精子DNA碎片指数(DFI)、精子线粒体膜电位(MMP)、精浆活性氧(ROS)和超氧化物歧化酶(SOD)水平以及透射电子显微镜下精子和精子线粒体超微结构。通过比较治疗前后组内和组间差异,分析聚精汤的临床疗效和作用机制。结果:共纳入并完成治疗随访60例患者,其中聚精汤治疗组30例,阳性对照组30例。聚精汤治疗组临床总有效率明显优于阳性对照组(76.8%vs 43.3%,P<0.05)。与治疗前比较,聚精汤治疗组治疗后前向运动精子百分率(PR%)、正常形态精子百分率、DFI和MMP均得到明显改善(P<0.05),精浆ROS水平有所下降(P>0.05),SOD水平明显提高(P<0.05);阳性对照组治疗后PR%、正常形态精子百分率、DFI和MMP亦有改善(P>0.05),精浆ROS水平下降不明显(P>0.05),SOD水平有所提高(P<0.05)。聚精汤治疗组治疗后PR%(42.68±15.86%)、正常形态精子百分率(3.66±1.72%)、DFI(16.61±4.20%)和MMP(61.79±8.61%)的改善均优于阳性对照组(P<0.05);聚精汤治疗组治疗后精浆ROS水平略低于阳性对照组(P>0.05),SOD明显高于阳性对照组(P<0.05)。通过透射电子显微镜观察发现聚精汤治疗后精子线粒体超微结构有明显改善。两组治疗后随访均未发现与药物相关的严重不良反应事件。结论:聚精汤可以显著提高弱畸形精子症患者PR%、正常形态精子百分率、MMP和精浆SOD水平,有效降低DFI和精浆ROS水平,并改善精子线粒体超微结构,可能通过抗氧化应激改善精子线粒体结构和功能途径发挥临床疗效机制;聚精汤临床治疗安全有效且疗效优于天然型维生素E软胶囊联合左卡尼汀口服液。

Objective:To observe the clinical efficacy and action mechanism of Jujing Decoction(JJD)in the treatment of asthenoteratozoospermia(ATZ)by comparing JJD with combined administration of the antioxidant stress drug and sperm energy metabolism agent.Methods:According to the inclusion criteria,we enrolled 67 male patients with ATZ in this randomized controlled clinical study and treated them by oral administration of JJD(the JJD group,n=34)or natural vitamin E combined with L-carnitine solution(the positive control group,n=33),both for 12 weeks.We collected the semen parameters,sperm DNA fragmentation index(DFI),sperm mitochondrial membrane potential(MMP),seminal plasma reactive oxygen species(ROS)and superoxide dismutase(SOD)levels from the patients,observed the ultrastructure of sperm mitochondria under the transmission electron microscope(TEM)before and after treatment,and analyzed the clinical efficacy and action mechanism of JJD by comparing the data obtained between the two groups.Results:Treatment and follow-up were completed in 60 of the cases,30 in the JJD and 30 in the positive control group.The total rate of clinical effectiveness was significantly higher in the JJD than in the positive control group(76.8%vs 43.3%,P<0.05).Compared with the baseline,the percentages of progressively motile sperm(PMS)and morphologically normal sperm(MNS),DFI and MMP were significantly improved(P<0.05),the level of seminal plasma ROS decreased(P>0.05),and that of SOD remarkably increased(P<0.05)after treatment with JJD;PMS,MNS,DFI and MMP were also improved(P>0.05),seminal plasma ROS decreased(P>0.05)and SOD increased(P<0.05)in the positive controls after medication.In comparison with the positive controls,the patients treated with JJD showed even more significant improvement in PMS([29.37±14.56]%vs[42.68±15.86]%,P<0.05),MNS([1.84±1.32]%vs[3.66±1.72%]%,P<0.05),DFI([32.66±5.23]%vs[16.61±4.20]%,P<0.05)and MMP([46.47±9.48]%vs[61.79±8.61]%,P<0.05),ROS([7.08±0.51]vs[5.06±0.52]μmol/L,P>0.05),and SOD([100.65±10.59]vs[139.05±14.71]U/ml,P<0.05).TEM revealed significantly improved ultrastructure of sperm mitochondria after treatment with JJD.No serious adverse reactions were observed in either group during follow-up.Conclusion:JJD,superior to natural vitamin E and L-carnitine oral solution,can safely and effectively increase the percentages of PMS and MNS,MMP and the level of seminal plasma SOD,reduce sperm DFI and seminal plasma ROS,and improve the ultrastructure of sperm mitochondria in patients with ATZ.The underlying mechanism of action may be related to its ability of improving the structure and function of sperm mitochondria via antioxidant stress.