Background. Chronic kidney disease condition requires regular dialysis; the patients have greater risk of sepsis and have high mortality rate compared to general people with sepsis. The adverse cardiac condition leads to mortality in subjects with sepsis. In the present work, we studied the consequences of chronic kidney damage by 5/6 nephrectomy on cardiac function in mice induced with sepsis and the mechanism involved. Methods. We used C57BL/6 mice and subjected them to 5/6 nephrectomy; after induction of chronic kidney damage, they were subjected to sepsis by either LPS treatment or by cecal ligation and puncture (CLP) method. The cardiac function test was done by echocardiography. Protein expression was done by western blot analysis. Results. The 5/6 nephrectomized mice showed significant increase in blood creatinine and urea levels compared to sham-operated mice; the mice also showed decreased ejection fraction and increased levels of phosphorylated IkBα and nuclear translocation of the NF-κB and inducible nitric oxide synthase (iNOS). When subjected to CLP and LPS treatment, the 5/6 nephrectomized mice augmented cardiac abnormalities and lung inflammation and increased plasma levels of TNF-α, IL-1, IL-12, and IL-18. Also, we evidenced increased levels of p-IKKα/β and Ikβα, NF-κβ, and iNOS. Treatment of IKK inhibitor VII in 5/6 nephrectomized mice after LPS administration or CLP attenuated these effects. Conclusion. Chronic kidney disease could lead to abnormal cardiac function caused by sepsis in mice; this may be due to increased expression of NF-κβ and iNOS in cardiac tissues.

中文翻译：

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IκB 激酶抑制剂 VII 可调节 5/6 肾切除小鼠脓毒症引起的过度炎症和心脏功能障碍。


背景。慢性肾脏病需要定期透析；与普通脓毒症患者相比，患者发生脓毒症的风险更大，死亡率也更高。不良的心脏状况导致脓毒症患者死亡。在目前的工作中，我们研究了5/6肾切除术造成的慢性肾损伤对脓毒症小鼠心功能的影响及其机制。方法。我们使用C57BL/6小鼠并对它们进行5/6肾切除术；在诱导慢性肾损伤后，通过LPS治疗或盲肠结扎穿刺（CLP）方法使他们患上败血症。通过超声心动图进行心功能检查。通过蛋白质印迹分析进行蛋白质表达。结果。与假手术小鼠相比，5/6肾切除小鼠的血肌酐和尿素水平显着升高；小鼠还表现出射血分数降低、磷酸化 IkB α水平升高、NF- κ B 和诱导型一氧化氮合酶 (iNOS) 核转位水平升高。当接受 CLP 和 LPS 治疗时，5/6 肾切除小鼠的心脏异常和肺部炎症加剧，血浆 TNF- α 、IL-1、IL-12 和 IL-18 水平增加。此外，我们还发现 p-IKK α / β和 Ik βα 、NF- κβ和 iNOS 水平升高。在给予 LPS 或 CLP 后，对 5/6 肾切除小鼠进行 IKK 抑制剂 VII 治疗可减弱这些作用。结论。慢性肾脏疾病可能导致小鼠脓毒症引起的心脏功能异常；这可能是由于心脏组织中 NF- κβ和 iNOS 表达增加所致。