Diacerhein Attenuates Sepsis-induced Pulmonary Vascular Endothelial barrier Dysfunction via Inhibition of Advanced Glycation End Products

Author:

Xu Jia1,Wei Lingyu1,Sun Zaiyuan2,Gong Wenqian1,Luo Minghao3,Peng Junnan4,Zhou Xiaomin5,Xu Xue1,Su Zedazhong6

Affiliation:

1. The First Affiliated Hospital of Sun Yat-sen University

2. The Seventh Affiliated Hospital of Sun Yat-sen University

3. First Affiliated Hospital of Chongqing Medical University

4. Second Affiliated Hospital of Chongqing Medical University

5. First People's Hospital of Yunnan Province

6. Guangdong Provincial People's Hospital

Abstract

Abstract AIM Acute lung injury in sepsis is a life-threatening clinical problem with high mortality and few treatment options, posing a significant challenge for clinicians. Powerful anti-inflammatory anthraquinone derivative dialcerhein (DIA) has numerous targets. The objective of this investigation is to ascertain whether DIA and potential molecular targets can protect mice against sepsis-induced deteriorate of the pulmonary vascular endothelial barrier. METHODS Cecal ligation and puncture (CLP) was used to induce sepsis in mice, followed by DIA administration. Survival rate, serum biochemical indicators and advanced glycation end products (AGEs), pulmonary vascular endothelial barrier function, glucose tolerance, and protein expression in lung tissue were all studied using molecular and biochemical approaches. RESULTS In septic mice lung tissue, DIA therapy normalized CLP-induced survival rate, vascular hyperpermeability, pulmonary vascular endothelial barrier dysfunction, inflammatory response, insulin tolerance test, AGEs level, and VE-cadherin phosphorylation level. Furthermore, AGEs and Scr interventions could greatly impair the therapeutic efficacy of DIA. CONCLUSION In this study, DIA alleviated pulmonary vascular endothelial barrier dysfunction in septic mice by regulating inflammation and lowering insulin resistance through AGEs inhibition. These findings showed that DIA could be a potential therapeutic for sepsis patients.

Publisher

Research Square Platform LLC

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