七氟醚通过风险信号通路改善大鼠肾缺血再灌注损伤

IF 0.6 4区 医学 Q4 PHARMACOLOGY & PHARMACY Tropical Journal of Pharmaceutical Research Pub Date : 2023-09-15 DOI:10.4314/tjpr.v22i8.10
Bo Wang, Xin Yan, Xin Zou
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引用次数: 0

摘要

目的:探讨七氟醚对大鼠肾缺血再灌注损伤(IRI)的影响及其对再灌注损伤挽救激酶(RISK)信号通路的调控作用。方法:将30只sd大鼠随机分为假手术组、模型组和七氟醚组,每组10只。模型组和七氟醚组造肾IRI模型,假手术组不结扎。采用苏木精和伊红(HE)染色检测肾损伤。检测血尿素氮(BUN)和血清肌酐(Scr)水平,并通过末端脱氧核苷酸转移酶介导的dUTP镍端标记(TUNEL)染色检测细胞凋亡。采用酶联免疫吸附试验(ELISA)分别测定大鼠肾组织和外周血丙二醛(MDA)含量和炎症因子。采用2,7-二氯氢双乙酸荧光素(DCFHDA)检测肾组织中活性氧(ROS)水平,Western blotting检测肾组织中凋亡和风险信号通路相关蛋白的表达。结果:与模型组比较,七氟醚组大鼠肾损伤明显减轻(p <0.01)。外周血BUN、Scr水平、肾组织细胞凋亡水平、肾组织MDA含量、ROS水平、白细胞介素-1β (IL-1β)、肿瘤坏死因子α (TNF-α)、IL-6含量、肾组织caspase-3蛋白含量均显著降低(p <0.01), IL-10含量、Bcl-2/Bax比值以及p- erk1 /2、p- akt和磷酸化糖原合成酶激酶3β (p <0.01)。结论:七氟醚通过激活肾IRI大鼠肾脏组织的RISK信号通路,抑制炎症因子的释放,降低肾细胞的ROS水平和凋亡,改善肾功能。因此,七氟醚是治疗IRI的潜在药物。
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Sevoflurane improves renal ischemia-reperfusion injury in rats through RISK signaling pathway
Purpose: To investigate the effect of sevoflurane on renal ischemia-reperfusion injury (IRI) in rats and its regulatory effect on reperfusion injury salvage kinase (RISK) signaling pathway.Methods: A total of thirty (30) Sprague-Dawley rats were randomly divided into sham, model and sevoflurane groups with 10 animals per group. Renal IRI models were created in model and sevoflurane groups, while sham group had no ligation. Renal injury was determined using hematoxylin and eosin (HE) staining. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels were assayed while apoptosis was determined via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Enzyme-linked immunosorbent assay (ELISA) was used to assess malonaldehyde (MDA) content and inflammatory factors in kidney tissues and peripheral blood, respectively. Reactive oxygen species (ROS) level was determined using 2,7-dichlorodi-hydro fluorescein diacetate (DCFHDA) while Western blotting was used to determine the expression of apoptosis- and RISK signaling pathway-related proteins in kidney tissues.Results: Compared to model group, renal injury in sevoflurane group rats was significantly alleviated (p < 0.01). The levels of BUN and Scr in peripheral blood, apoptosis level in kidney tissues, MDA content and ROS level in kidney tissues, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 content, and content of caspase-3 protein in kidney tissues were significantly reduced (p < 0.01), whereas IL-10 content, Bcl-2/Bax ratio and expression levels of p-ERK1/2, p-Akt and phosphorylated glycogen synthase kinase 3β (p-GSK-3β) were significantly increased (p < 0.01) in the sevoflurane group.Conclusion: Sevoflurane represses the release of inflammatory factors, lowers ROS level and apoptosis of renal cells and improves renal function through activation of RISK signaling pathway in kidney tissues of rats with renal IRI. Thus, sevoflurane is a potential agent for the treatment of IRI.
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期刊介绍: We seek to encourage pharmaceutical and allied research of tropical and international relevance and to foster multidisciplinary research and collaboration among scientists, the pharmaceutical industry and the healthcare professionals. We publish articles in pharmaceutical sciences and related disciplines (including biotechnology, cell and molecular biology, drug utilization including adverse drug events, medical and other life sciences, and related engineering fields). Although primarily devoted to original research papers, we welcome reviews on current topics of special interest and relevance.
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