ABSTRACT

We investigated the antioxidant, anti-inflammatory and anti-apoptotic effects of pregabalin (PREG) on lipopolysaccharide (LPS) induced sepsis related cardiotoxicity via NF-kβ pathways. We used 24 female Wistar albino rats divided into three groups: control, LPS treated and LPS + PREG treated. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-kβ)/p65, p-NF-kβ/p65, caspase-3 (Cas-3) and cleaved Cas-3 were measured in cardiac tissues and creatine kinase MB (CKMB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels were measured in blood samples. Also, Cas-3, granulocyte-colony stimulating factors (G-CSF), interleukin-6 (IL-6), serum amyloid A (SAA) and inducible nitric oxide synthase (iNOS) were measured immunohistochemically in heart and aorta tissue. In the LPS group; the levels of CKMB, AST, LDH, TOS, OSI increased and TAS decreased. TNF-α, p-NF-kβ/p65 and Cas-3 protein levels also increased in the LPS group. Immunohistochemical evaluation of the heart and aorta revealed a significant increase in the levels of Cas-3, G-CSF, SAA, IL-6 and iNOS in the LPS group. PREG treatment restored all measurements to near normal. LPS induced cardiovascular toxicity was due to inflammation, oxidative stress and apoptosis. PREG ameliorated the damage by inhibition of NF-kβ phosphorylation.

摘要

我们研究了普瑞巴林 (PREG) 通过 NF-kβ 通路对脂多糖 (LPS) 诱导的败血症相关心脏毒性的抗氧化、抗炎和抗凋亡作用。我们使用了 24 只雌性 Wistar 白化大鼠，分为三组：对照组、LPS 治疗组和 LPS + PREG 治疗组。总氧化状态（TOS）、总抗氧化状态（TAS）、氧化应激指数（OSI）、肿瘤坏死因子α（TNF-α）、核因子κβ（NF-kβ）/p65、p-NF-kβ/p65在心脏组织中测量了 caspase-3 (Cas-3) 和裂解的 Cas-3，并在血液样本中测量了肌酸激酶 MB (CKMB)、天冬氨酸转氨酶 (AST)、乳酸脱氢酶 (LDH) 水平。此外，Cas-3、粒细胞集落刺激因子 (G-CSF)、白细胞介素-6 (IL-6)、在心脏和主动脉组织中通过免疫组织化学方法测量血清淀粉样蛋白 A (SAA) 和诱导型一氧化氮合酶 (iNOS)。在 LPS 组中；CKMB、AST、LDH、TOS、OSI水平升高，TAS降低。LPS 组的 TNF-α、p-NF-kβ/p65 和 Cas-3 蛋白水平也增加。心脏和主动脉的免疫组织化学评估显示 LPS 组中 Cas-3、G-CSF、SAA、IL-6 和 iNOS 的水平显着增加。PREG 治疗使所有测量值恢复到接近正常。LPS 诱导的心血管毒性是由于炎症、氧化应激和细胞凋亡。PREG 通过抑制 NF-kβ 磷酸化来改善损伤。心脏和主动脉的免疫组织化学评估显示 LPS 组中 Cas-3、G-CSF、SAA、IL-6 和 iNOS 的水平显着增加。PREG 治疗使所有测量值恢复到接近正常。LPS 诱导的心血管毒性是由于炎症、氧化应激和细胞凋亡。PREG 通过抑制 NF-kβ 磷酸化来改善损伤。心脏和主动脉的免疫组织化学评估显示 LPS 组中 Cas-3、G-CSF、SAA、IL-6 和 iNOS 的水平显着增加。PREG 治疗使所有测量值恢复到接近正常。LPS 诱导的心血管毒性是由于炎症、氧化应激和细胞凋亡。PREG 通过抑制 NF-kβ 磷酸化来改善损伤。