基于JAK2/STAT3信号通路研究左归丸调控睾丸炎性微环境提高精子质量的作用机制  

Investigating the mechanism of Zuogui Pill in regulating testis inflammatory microenvironment and improving sperm quality through the JAK2/STAT3 signaling pathway

作　　者：任方楠 曹继刚[1] 萧闵[1] 王望 郝恒 REN Fang-nan;CAO Ji-gang;XIAO Min;WANG Wang;HAO Heng(Hubei University of Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学,湖北武汉430065

出　　处：《时珍国医国药》2025年第4期636-643,共8页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金青年项目(82104704)。

摘　　要：目的基于JAK2/STAT3信号通路研究左归丸调控先天肾虚大鼠睾丸炎性微环境,改善BTB通透性,提高精子质量的作用机制。方法采用CUMS应激法模拟孕鼠孕期恐应激,建立先天肾虚子代大鼠模型。通过行为学实验评估孕鼠模型,TUNEL染色法观察各组子代大鼠模型睾丸生精细胞凋亡情况,HE染色法观察睾丸组织病理微观结构,全自动精子分析仪检测精子密度及活动率,WB法检测睾丸组织JAK2、STAT3、Cx43蛋白表达,ELISA实验检测血清炎症因子IL-6、TNF-α水平。结果与空白组比较,模型组子代大鼠睾丸生精细胞异常凋亡,炎性细胞广泛浸润,精子密度、活动率均显著降低,血清IL-6、TNF-α水平及睾丸组织JAK2、STAT3蛋白表达量显著升高,连接蛋白Cx43表达量显著降低。与模型组比较,预防组子代大鼠睾丸各级生精细胞数量丰富,精子密度明显升高,精子活动率显著升高,血清IL-6、TNF-α水平及睾丸组织STAT3表达量显著降低,睾丸组织JAK2表达量明显降低,连接蛋白Cx43表达量显著升高。结论左归丸可能通过促进子代大鼠胚胎时期支持细胞类群增殖从而改善成年后生精细胞异常凋亡,抑制血清炎症因子IL-6、TNF-α对于JAK2/STAT3信号通路的持续激活,提高Cx43蛋白表达水平,恢复BTB通透性,达到提高精子质量的目的。Objective To explore the mechanism of Zuogui Pill(ZGP)in regulating the testicular inflammatory microenvironment,im⁃proving the blood-testis barrier(BTB)permeability,and the enhancing sperm quality in rats with congenital kidney deficiency based on the JAK2/STAT3 signaling pathway.Methods A rat model of congenital kidney deficiency was established using the chronic unpredicta⁃ble mild stress(CUMS)method to simulate the fear stress during pregnancy.Behavioral experiments were conducted to evaluate the pregnant rat models.TUNEL staining was used to observe the apoptosis of testicular spermatogenic cells in the offspring models.Hema⁃toxylin-eosin staining(HE)was used to observe the pathological microstructure of the testicular tissues.An automatic sperm analyzer was employed to measure sperm density and motility.Western blot(WB)was used to detect the protein expressions of JAK2,STAT3 and Connexin43(Cx43)in the testicular tissues,and enzyme-linked immunosorbent assay(ELISA)was used to measure serum in⁃flammatory factors,including interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)levels.Results Compared with the blank group,the model group showed abnormal apoptosis of testicular spermatogenic cells,widespread inflammatory cell infiltration,and significant reductions in sperm density and motility.Serum levels of IL-6 and TNF-α,as well as JAK2 and STAT3 protein expressions in the testicular tissues,were significantly increased,while Cx43 expression was significantly decreased.In the prevention group,com⁃pared with the model group,the number of spermatogenic cells at all stages in the testis was increased,sperm density and motility were significantly higher,serum IL-6 and TNF-αlevels,as well as STAT3 expression in testicular tissue,were significantly reduced,JAK2 expression in the testicular tissues was significantly decreased,and Cx43 expression was significantly elevated.Conclusion ZGP may im⁃prove the abnormal apoptosis of spermatogenic cells in adult rats by promoting the proliferation of supportiv

关 键 词：睾丸炎性微环境 左归丸 先天肾虚 血睾屏障 精子质量 

分 类 号：R285.5[医药卫生—中药学]