RESUMO
Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING-TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING-TBK1 signaling pathway and potential drug targets.
Assuntos
Injúria Renal Aguda , Modelos Animais de Doenças , Lipopolissacarídeos , Proteínas de Membrana , Proteínas Serina-Treonina Quinases , Sepse , Transdução de Sinais , Animais , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/tratamento farmacológico , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Sepse/complicações , Sepse/metabolismo , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Masculino , Rim/patologia , Rim/metabolismo , Rim/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Citocinas/metabolismoRESUMO
Background: Migraine, vestibular migraine (VM) and tension-type headache (TTH) are the most common disorders in dizziness and headache clinics, associated with dizziness or vertigo and postural imbalance, causing a substantial burden on the individual and the society. The objective of this research was to examine the presence of spontaneous nystagmus, comorbidity of benign paroxysmal positional vertigo (BPPV), and Tumarkin fall in patients; additionally, the study focused on assessing the patients' responses to bithermal caloric irrigation and video head impulse test (vHIT). Methods: Consecutive patients diagnosed with migraine, VM, and TTH according to the International Classification of Headache Disorders, third edition (beta version (ICHD-3ß)), who were referred to Dizziness and Headache Clinic were enrolled. BPPV and Tumarkin fall were assessed by questionnaires. The presence of BPPV was further evaluated through Dix-Hallpike or head roll maneuver, while spontaneous nystagmus was monitored using video-oculography during interictal period. Lastly, patients' responses to bithermal caloric irrigation and vHIT were analyzed. Results: There was a significantly higher incidence of spontaneous nystagmus in VM compared to both migraine and TTH. The drop attack episodes were slightly more frequent in VM than in TTH and migraine, though not statistically significant. The prevalence of BPPV was significantly higher in VM than in migraine and TTH. Unilateral vestibular paresis was more common in the VM group than in migraine and TTH. There was profound unilateral weakness (UW) in VM patients than in migraine, but no significant difference was found between VM and TTH. In VM, the percentage of saccades along with reduced vHIT gain was significantly higher than in migraine. Lastly, the percentage of abnormal response in vHIT was significantly lower than the percentage of abnormal UW in caloric irrigation across all groups. Conclusions: In VM patients, the prevalences of decompensated peripheral damage and BPPV were higher than in migraine and TTH patients as disclosed by the presence of peripheral spontaneous nystagmus and abnormal vHIT during the interictal period. Our findings suggest that the peripheral vestibular system acts as a significant mechanism in the pathogenesis of VM, and it might also be involved in migraine and TTH cases without vertigo symptoms.