Abstract
BackgroundAcute kidney injury (AKI) is a common disease that can develop into end-stage kidney disease. Sepsis is one of the main causes of AKI. Currently, there is no satisfactory way to treat septic AKI. Therefore, we have shown the protective function of Cul4a in septic AKI and its molecular mechanism.MethodsThe cellular and animal models of septic AKI were established by using lipopolysaccharide (LPS). Western blot (WB) was employed to analyze Cul4a expression. RT-qPCR was employed to test the expression of Cul4a, SOD1, SOD2, GPX1, CAT, IL-6, TNF-a, Bcl-2, IL1b, Bax and KIM-1 mRNA. ELISA was performed to detect the contents of inflammatory factors and LDH. CCK-8 was utilized to detect cell viability. Flow cytometry was utilized to analyze the apoptosis. DHE-ROS kit was used to detect the content of ROS.ResultsCul4a was down-regulated in cellular and animal models of septic AKI. Oxidative stress is obviously induced by LPS, as well as apoptosis and inflammation. However, these can be significantly inhibited by up-regulating Cul4a. Moreover, LPS induced the activation of the NF-kB pathway, which could also be inhibited by overexpression of Cul4a.ConclusionsCul4awas found to be a protective factor in septic AKI, which could inhibit LPS-induced oxidative stress, apoptosis and inflammation of HK-2 cells by inhibiting the NF-kB pathway.
Highlights
Acute kidney injury (AKI) refers to a syndrome in which a patient’s renal function is significantly declined rapidly due to various causes, and a series of clinical symptoms occur, including increased serum creatinine (Cr), decreased urine output, electrolyte disturbance, acidbase imbalance, etc
The expression of Cul4a in the LPS-treated HK-2 cells was detected through Western blot (WB)
We constructed the rat model of septic AKI and detected Cul4a expression in the kidney
Summary
AKI refers to a syndrome in which a patient’s renal function is significantly declined rapidly due to various causes, and a series of clinical symptoms occur, including increased serum creatinine (Cr), decreased urine output, electrolyte disturbance, acidbase imbalance, etc. Suffering from AKI can lead to increased demand for renal replacement therapy, increased risk of death, and more treatment costs, which will bring a heavy burden to patients and society [1,2,3]. A large clinical study showed that in critically ill patients, septic shock is the main factor in the onset of AKI, accounting for 47.5% of the total population [4]. Sepsis is a continuous and excessive inflammatory response and immunosuppression caused by pathogen invasion. It is an important factor for organ failure of the body and can lead to shock and even death of patients [5]. The fatality rate reaches 35% [6], which seriously threatens the life and health of patients [7]. Exploring new sepsis AKI treatment drugs is of great significance for alleviating kidney damage and saving patients’ lives and health
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