Kucuk Ahmet, Aksungur Nurhak, Halici Zekai, Tavaci Taha, Ozkaraca Mustafa, Tebrizi Behzat
Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum, Turkey.
Department of Clinical Pharmacology, Faculty of Medicine, Atatürk University, Erzurum, Turkey.
Inflammopharmacology. 2025 Sep;33(9):5435-5450. doi: 10.1007/s10787-025-01862-3. Epub 2025 Jul 29.
Given the elevated mortality rates and significant treatment costs associated with sepsis, characterized by a dysregulated host response to infection and life-threatening organ dysfunction, the search for treatment strategies involving new and potentially effective agents is essential. Sunitinib, a tyrosine kinase inhibitor, shows promise for mitigating increased inflammation in sepsis through its modulation of specific molecular pathways. This study investigates the effects of sunitinib in the treatment of sepsis.
Sepsis was induced in rats using the cecal ligation and puncture (CLP) model and sunitinib treatment was administered orally at various dosages. The effects of sunitinib treatment were evaluated through molecular and histopathological methods. The impact of sunitinib treatment on survival was analyzed using Kaplan-Meier survival analysis.
With low-dose treatment, sunitinib was observed to reduce the levels of proinflammatory cytokines, including interleukin-6, interleukin-8, and TNF-α. However, no reduction was observed with high-dose sunitinib in comparison to the sepsis group. Polymerase chain reaction results indicated that the NLRP3 inflammasome pathway was attenuated with low-dose sunitinib treatment. Furthermore, the extent of sepsis associated histopathological and immunohistochemical changes was reduced with sunitinib treatment, as demonstrated by hematoxylin and eosin staining and immunohistochemical analysis. Survival analysis revealed that the group receiving low-dose sunitinib had the highest survival rate.
Different sunitinib doses in sepsis treatment yield significantly different molecular results, histopathological outcomes, and survival rates. A comprehensive investigation of tyrosine kinase inhibitor drugs such as sunitinib in the treatment of sepsis will enhance the efficacy of sepsis therapies.
鉴于脓毒症死亡率高且治疗成本巨大，其特征为宿主对感染的反应失调及危及生命的器官功能障碍，寻找涉及新型且可能有效的药物的治疗策略至关重要。舒尼替尼是一种酪氨酸激酶抑制剂，通过调节特定分子途径，有望减轻脓毒症中炎症反应的增强。本研究调查舒尼替尼在脓毒症治疗中的作用。
采用盲肠结扎和穿刺（CLP）模型诱导大鼠发生脓毒症，并以不同剂量口服给予舒尼替尼治疗。通过分子和组织病理学方法评估舒尼替尼治疗的效果。使用Kaplan-Meier生存分析来分析舒尼替尼治疗对生存率的影响。
低剂量治疗时，观察到舒尼替尼可降低促炎细胞因子水平，包括白细胞介素-6、白细胞介素-8和肿瘤坏死因子-α。然而，与脓毒症组相比，高剂量舒尼替尼未观察到降低作用。聚合酶链反应结果表明，低剂量舒尼替尼治疗可使NLRP3炎性小体途径减弱。此外，苏木精和伊红染色及免疫组织化学分析表明，舒尼替尼治疗可减轻脓毒症相关的组织病理学和免疫组织化学变化程度。生存分析显示，接受低剂量舒尼替尼治疗的组生存率最高。
脓毒症治疗中不同剂量的舒尼替尼产生显著不同的分子结果、组织病理学结果和生存率。对舒尼替尼等酪氨酸激酶抑制剂药物在脓毒症治疗中的全面研究将提高脓毒症治疗的疗效。
