RESUMEN
In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.
Asunto(s)
Ácido Clorogénico , ADN Mitocondrial , Inflamasomas , Proteínas de la Membrana , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR , Nucleotidiltransferasas , Varicocele , Animales , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Ratas , Varicocele/tratamiento farmacológico , Varicocele/metabolismo , ADN Mitocondrial/metabolismo , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Nucleotidiltransferasas/antagonistas & inhibidores , Nucleotidiltransferasas/metabolismo , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratas Sprague-Dawley , Espermatogénesis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Homeostasis/efectos de los fármacos , Relación Estructura-Actividad , Estructura MolecularRESUMEN
OBJECTIVE: To prospectively evaluate the efficacy of Removing Stasis and Reducing Heat Formula in accelerating calculus clearance and improving lower urinary tract symptoms of patients with proximal ureteral calculi after ureteroscopic Ho:YAG laser lithotripsy. METHODS: A total of 138 patients with proximal ureteral calculi underwent ureteroscopic Ho:YAG laser lithotripsy by a single endocrinologist. Stone size varied from 10 to 15 mm. After operation, the patients were randomly divided into three groups: the control group (group A), tamsulosin group (group B), and Removing Stasis and Reducing Heat Formula group (group C). The treatment lasted for 4 weeks or until stone clearance. The primary and secondary outcomes of the three groups at follow-up were assessed. RESULTS: Of the 131 patients available for follow-up, 44 cases were in the group A, 45 in the group B, and 42 in the group C, respectively. The stone free rate at 2 weeks in the groups B and C were significantly higher than that in the group A (95.56%, 97.62% vs. 79.55%; all P<0.05). The ureteral colic rate and mean time of fragment expulsion were significantly reduced in the groups B (4.44% and 7.86±4.99 days) and C (2.43% and 6.76±4.37 days) compared with the group A (22.73% and 11.54±9.89 days, all P<0.05). On the day of double-J ureteric stent removal, the group C differed significantly from the group A in the total International Prostate Symptom Score, irritative subscore, obstructive subscore, and quality of life score (all P<0.05). CONCLUSION: Removing Stasis and Reducing Heat Formula in the medical expulsive therapy might be an effective modality for patients with calculus in the proximal uretera after ureteroscopic Ho:YAG laser lithotripsy.