Investigating the potential mechanism of Pioglitazone in Sepsis-Related brain injury through transcriptomics.

Autor: Zhang X; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030001, China. Electronic address: 463091997@qq.com., Li R; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: llirui123456@b.sxmu.edu.cn., Chen MY; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: cmy1234x@b.sxmu.edu.cn., Ye WQ; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: wenqianye@b.sxmu.edu.cn., Liang JZ; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: liang@b.sxmu.edu.cn., Yang WJ; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: yvette0919@b.sxmu.edu.cn., Yang F; School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China; Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, Shanxi Medical University, Taiyuan 030001, China. Electronic address: fanfan42@sxmu.edu.cn., Ji HM; The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan 030001, China; Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030001, China. Electronic address: jihongming1234@163.com.
Jazyk: angličtina
Zdroj: Gene [Gene] 2024 Dec 30; Vol. 931, pp. 148892. Date of Electronic Publication: 2024 Aug 24.
DOI: 10.1016/j.gene.2024.148892
Abstrakt: Sepsis-related brain injury (SRBI) refers to brain dysfunction and structural damage caused by sepsis, which is characterized by inflammation, oxidative stress, and destruction of the blood-brain barrier. Pioglitazone is a PPAR-γ agonist in which PPAR-γ acts as an inflammatory modulator, determining the relationship between PPAR-γ and SRBI and inflammatory state is critical for the disease. This study aimed to construct a drug-target-disease network for SRBI and Pioglitazone based on network pharmacology, and to investigate the therapeutic effect and potential mechanism of Pioglitazone in SRBI induced by lipopolysaccharide (LPS) in rats through transcriptomics. To establish a rat Model of SRBI by intraperitoneal injection of LPS (10 mg/kg): SD rats were divided into Control, Model (LPS), Pioglitazone, (LPS + Pioglitazone) and GW9662 group (LPS+GW9662). The effects and potential mechanisms of Pioglitazone in the treatment of SRBI were studied using biochemical indexes, pathological changes and transcriptome-sequencing (RNA-seq). RNA-seq results showed 620 DEGs between the Model and the Pioglitazone groups. Enrichment analysis involved multiple inflammatory response processes and chemokine receptor binding functions. TLR4 and CXCL10 in the Toll signaling pathway may play an important role in SRBI as important targets. Pioglitazone may ameliorate SRBI through the PPAR-γ/TLR4/CXCL10 pathway.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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