机构地区:[1]北京大学第三医院,北京100191 [2]北京大学第一医院,北京100034 [3]北京中医药大学研究生院,北京100029
出 处:《中国实验方剂学杂志》2024年第11期238-244,共7页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家自然科学基金项目(82104865);北京市科协青年人才托举工程项目(BYESS2023175);中华中医药学会青年人才托举工程项目(2022-QNRC2-A06);北京大学第三医院临床重点项目(BYSY2022068)。
摘 要:特发性少弱精子症(IO)在男性不育的诊疗中越来越受重视,氧化应激损伤直接影响精子质量和精子发生,是10的主要诱因之一。精子质膜磷脂因富含多不饱和脂肪酸,对活性氧(ROS)极为敏感,堆积的ROS易导致脂质过氧化,甚或诱导铁死亡。其次精子缺乏碱基切除修复途径的下游关键蛋白,难以修复氧化应激状态下大量的DNA氧化损伤。同时氧化应激状态下,精子调亡途径被级联激活,使其快速丧失活动能力。ROS还会通过串扰下丘脑-垂体-性腺轴,抑制睾酮生成,最终影响精子发生。五子衍宗丸是契合中医治疗IO“补益肾精,兼调阴阳”理论的经典名方,临床证实其可以改善IO患者精子形态、数量和运动能力,提高男性生育力。五子衍宗丸的药效物质研究主要包括建立中药特征图谱以实现质量控制,和探索有效成分作用靶点的药理学研究。研究发现其主要活性成分为黄酮类和苯丙素类化合物,金丝桃苷、毛蕊花糖苷、山奈酚和五味子醇甲作为其主要活性物质和质量控制成分,具有较强的抗氧化活性,且部分已应用于生殖内分泌疾病的研究中。雷公藤多苷是氧化应激导致IO的主要造模方式,其造成睾丸组织中多种脂质过氧化物堆积,同时损伤机体抗氧化能力。机制研究发现,五子衍宗丸可以抑制IO模型中过高的ROS水平,提高机体抗氧化能力,继而改善炎症状态,抑制细胞凋亡,同时促进睾酮生成,最终缓解氧化应激导致的精子质量下降和精子发生不足。Idiopathic oligoasthenospermia(IO)has been increasingly emphasized in the diagnosis and treatment of male infertility.Oxidative stress damage directly affects sperm quality and spermatogenesis,constituting a major causative factor of IO.Firstly,due to its high content of polyunsaturated fatty acids,the sperm plasma membrane is highly sensitive to reactive oxygen species(ROS),leading to lipid peroxidation accumulation and even inducing ferroptosis.Secondly,deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress.Simultaneously,under oxidative stress,the apoptotic pathway of sperm is cascade-activated,causing rapid loss of motility.ROS further disrupts the hypothalamic-pituitary-gonadal axis,inhibiting testosterone production and ultimately affecting spermatogenesis.Wuzi Yanzongwan,in line with traditional Chinese medicine theory of treating IO through"nourishing kidney essence and harmonizing Yin and Yang",clinically demonstrates its ability to improve sperm morphology,count,and motility,thereby enhancing male fertility.The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components.Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids.Specifically,compounds such as hyperin,acteoside,kaempferol,and schisandrin A are identified as the primary active substances and quality control components.These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders.Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO.It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity.Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated RO
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