Artesunate Inhibits Renal Ischemia Reperfusion-Stimulated Lung Inflammation in Rats by Activating HO-1 Pathway
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ORIGINAL ARTICLE
Artesunate Inhibits Renal Ischemia Reperfusion-Stimulated Lung Inflammation in Rats by Activating HO-1 Pathway Zhaohui Liu ,1,3 Junjie Zhang,2 Shitong Li,2 and Jihong Jiang2
ABSTRACT— Artesunate (AS), a semi-synthetic derivative of Artemisia, has been shown to exert a wide range of pharmacological effects, such as anti-inflammatory and antioxidant functions. However, the protective functions of AS on renal ischemia reperfusion injury (RIR)-stimulated lung inflammation remain unclear. In this research, acute lung injury (ALI) was stimulated by renal ischemia reperfusion injury (RIR). AS (15 mg/kg) was intraperitoneal administrated to rat 1 h before RIR stimulation. Serum and pulmonary NO, MDA, IL-6, MIP2, and PGE2 levels, arterial blood gas and biochemistry, lung wet/dry weight ratio and MPO activity, total cell number and protein concentration in BALF, tissue histology, and NF-κB expression were determined. The results indicated that serum and pulmonary NO, MDA, IL6, MIP-2, and PGE2 levels, lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF enhanced after RIR stimulation. These alterations were mitigated by AS. AS attenuated lung wet/dry weight ratio and MPO activity, total cell number, and protein concentration in BALF. AS attenuated RIR-stimulated pulmonary NFκB phosphorylation. In addition, these previously mentioned actions of AS were antagonized by suppressing HO-1 pathway. However, RIR-stimulated arterial blood gas and biochemistry and lung histopathology were also attenuated by AS. In summary, AS inhibited RIRstimulated lung inflammation by activating HO-1 pathway. KEY WORDS: artesunate; renal ischemia reperfusion injury; acute lung injury; HO-1; NF-κB.
INTRODUCTION Renal ischemia reperfusion injury (RIR) is a common clinical syndrome of kidney inflammation responses with a high rate of complications and death [1]. RIR can result in remote organ injury such as the liver, heart, and lung [2–4]. Lung inflammation are the most common complication 1
Department of Anesthesiology, Cangzhou Central Hospital, No.16 Xinhua West Road, Yunhe District, Cangzhou, Hebei, China 2 Department of Anesthesiology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 3 To whom correspondence should be addressed at Department of Anesthesiology, Cangzhou Central Hospital, No.16 Xinhua West Road, Yu n h e D i s t r i c t , C a n g z h o u , H e b e i , C h i n a . E - m a i l : [email protected]
that caused by multiple ischemia reperfusion injury (IR) [5–7]. This experimental model was extensive used to investigate the underling mechanisms of lung inflammation and exploit new lung-protective drugs [1]. Previous reports have demonstrated that RIR-stimulated inflammatory molecules releases in rat model of lung inflammation [8–10]. These inflammatory molecules resulted in lung tissue edema and Pathological damage [11]. Heme oxygenase-1 (HO-1) is a kind of antiinflammation protein that plays an important role in the
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