BACKGROUND:Oligoasthenozoospermia (OAS) is one of the main causes of male infertility. Studies have shown that ginsenoside Rb1 (GRb1) and Lycium barbarum polysaccharide (LBP) have great potential in treating OAS. This study aims to investigate the effects of combined GRb1 and LBP treatment on OAS and the underlying molecular mechanisms. METHODS:The Tripterygium wilfordii polyglycoside (GTW)-induced mouse model and H2O2-induced cell model were intervened with GRb1 and LBP. HE staining and Johnson score were used to evaluate the degree of testicular injury. Then, sperm quality was evaluated, and the levels of sperm-related hormones were measured. The regulatory effect of GRb1 and LBP on oxidative stress in OAS mice and cells was explored. In addition, total zinc content in testicular tissues and GC-2 cells was measured, and the mRNA and protein expression levels of zinc transporter 3 (ZnT3) were detected. RESULTS:In the OAS model of mice treated with GRb1 and LBP, the coefficient of testis and epididymis were increased, and the degree of damage and sperm quality were significantly improved. Serum levels of T, LH, and FSH were increased in mice. Moreover, inhibition of ZnT3 signaling increased total intracellular zinc content in GC-2 cells. Overexpression of ZnT3 reversed the inhibitory effects of the combination of GRb1 and LBP on oxidative stress and the therapeutic effects in OAS mice. CONCLUSION:The combined treatment of GRb1 and LBP could inhibit oxidative stress response by down-regulating ZnT3 signaling, thereby improving OAS mice. This provided a new strategy for the drug treatment of OAS.

背景  复发性流产（RSA）是常见的生殖障碍性疾病，在胚胎植入过程中，子宫内膜发生上皮间充质转化（EMT），RSA的发生与该过程减弱密切相关。子宫内膜来源外泌体及其携带的miRNA参与细胞间通讯，影响细胞EMT，与RSA关系密切，但具体作用机制尚不明确。目的  本研究聚焦于外泌体在细胞EMT中的功能，通过实验验证子宫内膜来源外泌体及其分泌的miRNA-221对RSA小鼠子宫内膜细胞EMT的调控作用。方法  2021年10月—2022年5月，选取SPF级、健康8周龄雌性小鼠24只，随机选取12只作为正常对照组，剩余12只小鼠制作RSA模型，造模结束后雌雄合笼，妊娠第4日处死雌性小鼠，分离和培养子宫内膜上皮细胞并收集外泌体，通过透射电镜和WB进行外泌体鉴定；通过CCK8、Transwell和流式细胞术检测外泌体干预前后两组细胞增殖、侵袭、迁移能力；细胞EMT相关蛋白（E-cadherin、N-cadherin、Vimentin、MMP7、MMP9）及外泌体标志蛋白（CD63、CD81、TSG101）的表达；外泌体处理后的细胞EMT标志蛋白（CD24-APC、CD44-FITC）的表达；转染miRNA-221模拟物和抑制物分析外泌体源性miRNA-221对小鼠子宫内膜上皮细胞EMT的作用，并通过WB和双荧光素酶报告基因检测进行分析。结果  RSA组小鼠的子宫内膜上皮细胞具有异常的EMT，小鼠子宫内膜上皮细胞能够分泌外泌体。添加外泌体的RSA组细胞增殖率、迁移能力、侵袭能力、CD44+/CD24+表达水平高于细胞上清液RSA组（P<0.05）。与细胞上清液RSA组相比，添加外泌体的RSA组细胞的EMT标志蛋白E-cadherin水平升高，间质样标志蛋白N-cadherin和Vimentin以及基质标志蛋白MMP7、MMP9蛋白水平降低（P<0.05）。RSA组miR-221表达水平低于正常对照组（P<0.05）。与随机miRNA相比，miRNA-221模拟物激活了PI3K-AKT通路、NF-kB通路和p38通路（P<0.05）。与随机miRNA相比，miRNA-221模拟物降低了PTENmRNA的表达水平（P<0.05），而miRNA-221抑制剂转染则增加了PTENmRNA的表达水平（P<0.05）。结论  子宫内膜来源外泌体miRNA-221可通过负向调控Pten基因，激活PI3K-AKT通路，促进子宫内膜上皮细胞EMT，影响RSA妊娠结局。

Background Semen Cuscutae and Fructus Lycii (SC-FL) is known for its potential therapeutic effects on spermatogenesis dysfunction. However, the underlying mechanisms of SC-FL in alleviating spermatogenesis dysfunction is still being elucidated. Purpose This study aimed to explore the effects of SC-FL on spermatogenesis dysfunction and investigate the involved mechanisms, specifically focusing on the modulation of oxidative stress and ferroptosis. Methods A mouse model of spermatogenesis dysfunction was induced by tripterygium glycosides, followed by treatment with SC-FL. Assessment of testicular spermatogenic function in the mice was performed alongside lipidomics analysis to investigate the metabolic mechanisms of SC-FL. The effects on oxidative stress and ferroptosis-related markers were evaluated, the chemical constituents of SC-FL were identified using liquid chromatography-mass spectrometry, and network pharmacology analysis was carried out. Additionally, an in vitro model of spermatogenesis dysfunction was established using triptolide-induced GC-1 cells, which were treated with Lycium barbarum polysaccharides (LBP) and flavonoids from Semen Cuscutae (FSC) to explore their impact on cell damage, oxidative stress-mediated damage, and ferroptosis. Results SC-FL improved the mouse model of spermatogenesis dysfunction by inhibiting oxidative stress-mediated ferroptosis. In vitro experiments demonstrated that LBP and FSC relieved GC-1 cell damage, with their mechanisms also associated with the inhibition of oxidative stress-mediated ferroptosis. Conclusion SC-FL alleviates spermatogenesis dysfunction in animal and cell models, potentially through the modulation of the Nrf2/HO-1 signaling pathway, which consequently inhibits oxidative stress-mediated ferroptosis in spermatogonial cells.

BackgroundStroke is a devastating global health issue, with high mortality and disability rates. The increasing prevalence of male infertility among reproductive-aged men has become a growing concern worldwide. However, the relationship between male infertility and stroke incidence remains uncertain. This study aimed to address this knowledge gap by employing a Mendelian randomization (MR) approach.MethodUtilizing genetic instrumental variables derived from a genome-wide association study (GWAS) on male infertility and stroke, a two-sample MR design was implemented. Five different analysis methods, with inverse-variance weighted as the primary approach, were used to examine the genetic causal associations between male infertility and various stroke subtypes. Heterogeneity analysis, pleiotropy tests, and leave-one-out validation were conducted to assess heterogeneity, evaluate pleiotropy, and ensure the robustness of the findings.ResultThe results indicate a potential lower risk of small vessel stroke associated with male infertility (odds ratio, 95% confidence interval: 0.82, 0.68 to 0.99, p=0.044), although no significant impact on other stroke subtypes was observed. The study exhibited low heterogeneity and no apparent pleiotropy; however, the stability of the results was not optimal.ConclusionMale infertility might potentially confer a protective effect against small vessel stroke risk. Caution is warranted due to potential confounding factors. Additional studies are necessary to confirm these findings and provide further validation.

随着生活和社会环境的改变及生活工作压力的增加,我国男性生育能力显著下降,男性不育症发病率逐年增高,给男科医生带来了前所未有的挑战和治疗难题.中医药治疗男性不育症具有明确疗效,临床上应用广泛,为了明确中医药在男性不育症的不同种类及不同阶段做起的作用,中华中医药学会组织邀请了男科临床一线的西医与中医青年优秀专家,围绕特发性少、弱、畸形精子症、精液液化异常、精索静脉曲张、免疫性不育、提高辅助生殖技术成功率、改善抑郁焦虑状态等6个方面进行了讨论.就中医治疗的优点、特色、短板及优势病种、优势环节进行了深入探讨,针对男性不育症的各种病因及相关环节的治疗进行了梳理与归纳.男性不育症由于病因不完全明确及发病机制复杂等原因,单纯西医治疗不能达到较好的疗效,而中医药以整体观为核心,改善功能性疾病是学科优势,同时可以对应多靶点、多病因,并且有内治外治等综合性疗法,因此中医治疗及中西医医结合治疗男性不育症,在临床上应用广泛.该文总结了纯中医治疗及中西医结合治疗的优势病种和优势环节,罗列了相关病种的中西医治疗建议,以期让更多男科医生了解中医的治疗效应及优势能够实现中西借鉴、沟通融合,在临床实际诊疗中给患者提供优效、个性化的治疗方案,从而提高男性不育症的疗效.

目的 探讨填精通络汤联合他达拉非治疗2型糖尿病勃起功能障碍(DIED)患者的临床效果.方法 选取2019年10月至2020年12月北京中医药大学东直门医院男科连续诊治的82例2型DIED患者作为研究对象.采用随机数字表法分为治疗组和对照组,各41例.治疗组采用填精通络汤联合他达拉非治疗,对照组单独采用他达拉非治疗.比较两组治疗前后国际勃起功能指数-5(IIEF-5)评分、中医证候评分、临床疗效及睾酮、雌二醇、内皮素-1、一氧化氮水平.结果 治疗后,两组IIEF-5评分均较治疗前明显改善,且治疗组改善情况优于对照组,差异具有统计学意义(P<0.05);治疗组中医证候评分较治疗前明显改善,且优于对照组,差异具有统计学意义(P<0.05);治疗后,两组睾酮、雌二醇、内皮素-1及一氧化氮水平均较治疗前明显改善,且治疗组改善情况优于对照组,差异具有统计学意义(P<0.05);治疗组治疗总有效率优于对照组,差异具有统计学意义(P<0.05).结论 填精通络汤联合他达拉非能有效改善2型DIED患者的勃起功能,可能与提高一氧化氮及睾酮水平,降低内皮素-1水平有关.

The development and progression of the complications of chronic diabetes mellitus are attributed not only to increased blood glucose levels but also to glycemic variability. Therefore, a deeper understanding of the role of glycemic variability in the development of diabetic complications may provide more insight into targeted clinical treatment strategies in the future. Previously, the mechanisms implicated in glycemic variability-induced diabetic complications have been comprehensively discussed. However, endothelial dysfunction and platelet hyperactivation, which are two newly recognized critical pathogenic factors, have not been fully elucidated yet. In this review, we first evaluate the assessment of glycemic variability and then summarise the roles of endothelial dysfunction and platelet hyperactivation in glycemic variability-induced complications of diabetes, highlighting the molecular mechanisms involved and their interconnections.

目的 探讨应用来曲唑联合高糖高脂饮食的方法构建多囊卵巢综合征伴胰岛素抵抗(polycystic ovarian syndrome-insulin resistance,PCOS-IR)大鼠模型.方法 6周龄雌性SD大鼠20只,普通饲料适应性喂养1周后,随机数字表法选取10只作为对照组,其余10只作为模型组.对照组给予普通饲料,模型组给予高糖高脂饲料喂养28 d.于喂养第8天,模型组大鼠开始每日用0.4 mL溶于1％(质量分数)羧甲基纤维素溶液(carboxymethyl cellulose solution,CMC)的来曲唑液(1 mg·kg-1·d-1)灌胃,对照组灌服等体积CMC溶液,连续灌胃21 d.自灌胃第7天起,每日晨行阴道涂片,观察阴道脱落细胞的周期变化,判断动情周期,直至实验结束.灌胃结束后,测量体质量,尾静脉采血测定大鼠空腹血糖(fasting blood glucose,FBG),ELISA法测定血清促黄体生成素(luteinizing hormone,LH)、促卵泡生成素(follicle stimulating hormone,FSH)、血清睾酮(testosterone,T)、空腹胰岛素(fasting insulin,FINS)浓度,并计算LH/FSH比值、胰岛素敏感指数(insulin sensitivity index,ISI)和胰岛素抵抗指数(insulin resistance index,HOMA-IR).留取卵巢组织,应用HE染色观察卵巢组织形态.结果 与对照组比较,模型组大鼠体质量、FBG、FINS、T、LH浓度、HOMA-IR指数、LH/FSH比值均明显升高,FSH及ISI浓度显著降低,差异均有统计学意义(P<0.01);阴道涂片显示,模型组大鼠动情周期均消失;对照组卵巢局部组织形态正常,模型组呈典型多囊样改变.结论 应用高糖高脂联合来曲唑灌胃的方法,可以成功构建PCOS-IR大鼠模型,模型大鼠出现明显的胰岛素抵抗、特征性的多囊卵巢组织及性激素改变.

目的:基于网络药理学和实验验证,探讨温肾养血方提高高龄雌鼠子宫内膜容受性的有效成分、作用靶点及可能的作用机制.方法:基于BATMAN-TCM和整合药理学平台对温肾养血方中的中药成分及药物靶标进行检索;以"anovulatory sterility"和"anovulatory infertility"为关键词,通过人类孟德尔遗传数据库(OMIM)和GeneCards数据库,对排卵障碍性不孕症靶标进行搜集;基于STRING数据库中的蛋白质-蛋白质相互作用(PPI)数据库,并通过Cytoscape构建温肾养血方成分靶标及排卵障碍性不孕症靶标核心网络;基于DAVID数据库中基因本体(GO)和京都基因与基因组百科全书(KEGG)对共有靶标进行功能和通路分析,并建立"中药-成分-靶标-通路"分子网络,对核心靶点进行动物实验验证.结果:共获得化学成分253个,药物靶标326个,疾病靶标819个,共有靶标74个.GO和KEGG对共有靶标进行功能和通路分析结果显示,共有靶标主要参与了一氧化氮生物合成过程的正调控、细胞增殖的正调控、对雌二醇的反应、老化、氧化应激反应、血管生成等生物学过程.对GO过程中氧化应激反应以及KEGG前20中的5个重要通路进行分析,通过构建"中药-成分-靶标-生物学过程/通路"多维网络发现,共20种中药41种化学成分,这些成分通过影响35个靶标参与了低氧诱导因子-1(HIF-1)信号通路,肿瘤坏死因子(TNF)信号通路,叉头框蛋白O(FOXO)信号通路,Toll样受体(TLR)信号通路,磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路.动物实验结果显示,温肾养血方可提高高龄雌性ICR小鼠子宫磷脂酰肌醇3-激酶(PI3K),磷酸化(p)-PI3K,Akt,p-Akt,叉头框蛋白O3A(FoxO3A)和p-FoxO3A的表达量.结论:温肾养血方通过影响Akt1,双氧化酶-2(DUOX2),表皮生长因子受体(EGFR),血红素加氧酶-1(HMOX1),髓过氧化物酶(MPO)等靶标干预氧化应激及PI3K/Akt/FoxO3A信号通路提高高龄雌鼠子宫内膜容受性.

The prethrombotic state (PTS) is a possible cause of recurrent spontaneous abortion (RSA). The aim of this study was to identify serum biomarkers for the detection of RSA with PTS (PSRSA). A Quantibody array 440 was used to screen novel serum-based biomarkers for PSRSA/NRSA (RSA without PTS). Proteins differentially expressed in PSRSA were analysed using bioinformatics methods and subjected to a customized array and enzyme-linked immunosorbent assay (ELISA) validation. We used receiver operating characteristic to calculate diagnostic accuracy, and machine learning methods to establish a biomarker model for evaluation of the identified targets. 20 targets were selected for validation using a customized array, and seven targets via ELISA. The decision tree model showed that IL-24 was the first node and eotaxin-3 was the second node distinguishing the PSRSA and NRSA groups (an accuracy rate of 100% and an AUC of 1). Epidermal growth factor (EGF) as the node distinguished the PSRSA and NC groups (an accuracy rate of 100% and an AUC of 1). EGF as the node distinguished the NRSA and NC groups (an accuracy rate of 96.5% and an AUC of 0.998). Serum DNAM-1, BAFF, CNTF, LAG-3, IL-24, Eotaxin-3 and EGF represent a panel of promising diagnostic biomarkers to detect the PSRSA.

目的 研究西洋参茎叶总皂苷(PQS)对多囊卵巢综合征伴胰岛素抵抗(PCOS-IR)大鼠的作用效应及机制.方法 建立PCOS-IR大鼠模型,分为正常组、模型组、PQS低剂量组(30mg/kg)和PQS高剂量组(60mg/kg),每组10只.给药4周后,ELISA法检测血清睾酮(T)、促卵泡刺激素(FSH)、促黄体生成素(LH)、空腹血糖(FBG)、胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR);HE染色观察卵巢组织形态学变化;免疫组化检测卵巢组织Bcl-2和Bax表达;Western blot法检测PI3 K、p-PI3 K、Akt、p-Akt蛋白表达.结果 与正常组比较,模型组大鼠出现典型多囊样改变,血清T、LH水平及LH/FSH比值、FINS及HOMA-IR指数均显著升高,卵巢组织中Bcl-2、p-PI3 K、p-Akt表达显著减少,Bax表达显著升高;与模型组比较,PQS组大鼠卵巢组织多囊样改变显著改善,血清T、LH水平及LH/FSH比值、FINS及HOMA-IR指数显著降低,卵巢组织中Bcl-2、p-PI3 K、p-Akt表达显著升高,Bax表达显著降低.结论 PQS对PCOS-IR大鼠具有显著治疗效应,机制可能与激活卵巢组织PI3 k/Akt信号通路,调控Bcl-2与Bax分子的表达相关.

男性在生殖过程中的主要作用是提供精子,研究男性生殖功能最关键的就是研究精子发生.精子发生指的是睾丸生精小管内的精原干细胞分化为成熟精子的一系列精密复杂的过程.在睾丸支持细胞、间质细胞、其他物质和因子的共同参与下,各级生精细胞经过连续不断地增殖、分裂和分化,以及圆形精子细胞的成熟和形态变化,最终形成精子释放到睾丸小管内.睾丸的血睾屏障等结构、生精细胞和支持细胞等细胞在精子发生过程中均起着重要作用,而酶、激素、信号因子等一系列因素也在这个过程中起重要的调节作用,影响精子质量和数量,从而影响生育能力.本文从分子生物学的层面,将精子发生过程中生精细胞增殖和凋亡的过程、相关因子及通路进行整理和综述,以期为相关研究提供依据.

新冠疫情牵动着所有人的心,全国人民众志成城、共克时艰,疫情防控取得了不小的成效.但新冠疫情并未随着2020年的结束而终结.为了尽早控制住新冠疫情,疫苗的研发也一早就在进行中.2020年12月31日,中国首个新冠疫苗获批上市,全民免费接种.

近年来男科疾病的发病率呈现明显增长趋势,而传统的中医学在男科领域未形成完善的理论体系,虽然男科病种相对较少,但机制复杂,因此需要提高和改进男科疾病的临床疗效,以满足患者就诊的需求.为此,中华中医药学会组织中西医男科专家一起进行探讨,邀请中西医临床一线的青年优秀专家,共同针对男科疾病领域探讨中医及中西医结合治疗的临床优势病种,如慢性前列腺炎、男性不育症、良性前列腺增生、勃起功能障碍、早泄等,明确西医诊断,规范中医临床辨证诊疗,制定出中医西医公认的、融合的诊疗方案,提供优势病种的中西医治疗建议,中医哪些疾病有优势,哪些病程有优势,何时适合中医治疗,何时该采用西医治疗、手术治疗等问题,形成专家共识,同时也为中医临床提供参考依据,充分发挥中医药优势,提高男科疾病的诊疗效果,给患者提供精准的、个性化的和最优化的治疗方案,同时把中医的优势发挥淋漓尽致,这样中医也才能立得住,才能创新,才能发展.

目的 运用转录组学技术探讨雷公藤多苷致小鼠生殖毒性的机制.方法 以C57小鼠为研究对象,采用雷公藤多苷(GTW)40mg/kg每日灌胃干预4周后,比较模型组(GTW组)与空白组(NC组)小鼠的睾丸组织病理变化、精子浓度及活动力,并利用RNA-seq技术对睾丸组织进行转录组测序,比较GTW组与NC组之间的基因表达差异.结果 与NC组相比,GTW组小鼠睾丸呈现显著的生精障碍,主要表现在粗线期精母细胞及之后阶段的生精细胞大量缺失,精子浓度及活动力显著下降.测序结果表明共有15563条差异表达基因,其中上调基因7821条,下调基因7742条.功能分析结果显示,差异基因所涉及的GO生物学中的生物过程有细胞分化、细胞周期、凋亡过程等;细胞组分有细胞膜、细胞质、细胞核等;分子功能有ATP合成、蛋白合成、DNA合成等.KEGG富集的信号通路与生精相关的主要有磷脂酰肌醇3-激酶/丝氨酸-苏氨酸激酶(PI3K/Akt)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、GTP结合蛋白(Ras)信号通路、环磷酸腺苷(cAMP)信号通路等.结论 雷公藤多苷能够多途径影响精子的发生,主要的信号通路与细胞的增殖与凋亡相关.

目的:观察温肾养血颗粒对卵巢储备功能低下(DOR)模型大鼠卵巢储备功能及子宫内膜形态的影响.方法:雌性SD大鼠110只,随机选取20只作为对照组,其余90只采用雷公藤多苷片50mg·kg-1·d-1连续灌胃2周的方法建立DOR大鼠模型.将造模成功的80只大鼠随机分为模型组、温肾养血颗粒低剂量组(6g·kg-1·d-1)、温肾养血颗粒高剂量组(12g·kg-1·d-1)和补佳乐组(0.12mg·kg-1·d-1),每组20只.连续灌胃2周后取材,HE染色观察卵巢及子宫内膜组织学变化,进行卵泡计数并测定子宫内膜厚度;ELISA法检测大鼠血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、孕酮(P)、泌乳素(PRL)、抗苗勒管激素(AMH)、抑制素B(INHB)水平.结果:与对照组比较,模型组大鼠卵巢组织中生长卵泡总数显著减少,闭锁卵泡显著增多,子宫内膜厚度显著降低,血清FSH、LH水平显著升高,E2、AMH及INHB水平显著降低(P＜0.01).与模型组比较,温肾养血颗粒高、低剂量组和补佳乐组大鼠的卵巢组织形态学显著改善,生长卵泡总数显著增加,闭锁卵泡数显著减少,子宫内膜厚度显著增加,同时血清FSH、LH水平显著降低,E2、AMH及INHB水平显著升高(P＜0.01,P＜0.05).结论:温肾养血颗粒能够显著改善DOR模型大鼠的卵巢储备功能及子宫内膜形态.

一般情况下,"集中优势兵力"是一种科学的战术.所以,夫人久久未能怀孕,很多男性朋友便开始怀疑是不是自己的"兵力"不够强劲有力,觉得平时进行的性生活白白地浪费了精力和体力,尤其是浪费了精子.因此,男性朋友会选择减少夫妻生活来为自己"保精",而只在妻子排卵时"集中优势兵力".那么,长时间节制性生活可以增加生育机会吗?

Ethnopharmacological relevance: Semen Cuscutae and Fructus Lycii (SC-FL) is a commonly used herbal pair for male infertility treatment. Studies have found that the mechanism of SC-FL treatment may be related to repairing the blood-testis barrier (BTB). The application of network pharmacology can be used to explore the correlation between medicines and diseases and predict the potential pharmacological mechanisms of SC-FL. Aim of the study: This study aimed to explore the specific effects and mechanisms of SC-FL in repairing the BTB and initially revealed the mechanism of Chinese medicine treating male infertility through network pharmacology and animal experiments. Materials and methods: We searched databases using the network pharmacology method and performed mass spectrometry analysis. We analyzed and predicted the active ingredients, targets and key pathways of SC-FL in male infertility treatment. Then, we designed animal experiments to verify the results. Thirty-six Sprague-Dawley rats were randomly divided into the normal control group (NC group), spermatogenic dysfunction group (SD group) and SC-FL treatment group (SCFL group). Glucosides of Tripterygium wilfordii Hook. F (GTW) (40 mg/ kg/d) was administered for 4 weeks to generate a spermatogenic dysfunction model. The rats in the SCFL group were given the SC-FL suspension (6 g/kg/d) daily. After 4 weeks of treatment, we detected the sperm quality of each group of rats and observed the cell morphology. Western blotting and qRT-PCR were used to detect the expression of BTB-related proteins in testicular tissues. Results: 213 chemical ingredients of SC and FL were retrieved from the TCMSP database, and 54 effective chemical ingredients were obtained. Mass spectrometry analysis showed the above results were credible. Then, we identified 44 potential targets for the treatment of male infertility, and we plotted a network diagram of the interaction network between the core targets and a diagram of herbal medicine-active ingredient-target-disease interactions. The target genes were enriched according to biological functions, and 22 biological processes, 49 cellular components, 1487 molecular functions, and 122 signaling pathways were obtained. The results of the animal experiments showed that the sperm concentration and motility of the SCFL group were significantly improved compared with those of the SD group. Compared with those in the SD group, the structure and morphology of the Sertoli cells and seminiferous tubules of rats in the SCFL group improved, and the number of spermatogenic cells increased significantly. Western blotting and qRT-PCR results showed that compared with that in the SD group, the expression of p38 MAPK decreased significantly, and the expression of c-Jun, Occludin, ZO-1 and connexin 43 increased significantly in the SCFL group. Conclusion: We predicted that the active ingredients of SC-FL can treat male infertility by interacting with the core targets JUN, IL6, MAPK1, TP53, MYC, CCND1, AR, EGF, FOS, and MAPK8, and the possible mechanism is related to the MAPK signaling pathway. SC-FL can regulate the MAPK pathway and affect the expression of Occludin, ZO-1 and connexin 43 to repair damaged BTB and improve spermatogenic dysfunction induced by GTW, which may be one of the possible mechanisms.

目的 运用网络药理学方法分析川芎嗪和芍药苷治疗糖尿病血管并发症的潜在作用机制.方法 检索SwissTargetPredic-tion ver 2019、Batman-TCM、PharmMapper ver 2017、ZINC、SEA、GeneCards、DrugBank 5.0、DisGenet、String v11数据库,筛选川芎嗪和芍药苷化学成分作用靶点以及糖尿病血管并发症的相关靶点;应用Cytoscape 3.2.1软件,构建川芎嗪和芍药苷成分靶点-疾病靶点网络;通过GO和KEGG富集分析预测川芎嗪和芍药苷治疗糖尿病血管并发症的潜在作用机制.结果 从川芎嗪和芍药苷中分别筛选出成分靶点103个和168个,将这些成分靶点与4662个糖尿病血管并发症靶点取交集得到146个靶点,网络拓扑分析得到TP53、HSP90AA1、STAT3和ANXA14个核心靶点,可能为川芎嗪和芍药苷治疗糖尿病血管并发症的重要靶点;GO和KEGG富集分析显示川芎嗪和芍药苷治疗糖尿病血管并发症的可能通路是Neuroactive ligand-receptor interaction,Calcium signaling pathway,Serotonergic synapse,Inflammatory mediator regulation of TRP channels,cGMP-PKG,Dopaminergic synapse.结论 初步揭示了川芎嗪和芍药苷治疗糖尿病血管并发症的作用通路及重要活性靶点,为开发更好地治疗糖尿病血管并发症候选药物的活性成分提供参考依据.