Emodin alleviates lung injury via the miR-217-5p/Sirt1 axis in rats with severe acute pancreatitis

被引:1
作者
Zhang, Zhihang [1 ,2 ,3 ]
Luo, Yalan [1 ]
Zhuang, Xijing [4 ]
Gao, Haifeng [5 ]
Yang, Qi [6 ]
Chen, Hailong [1 ,3 ]
机构
[1] Dalian Med Univ, Affiliated Hosp 1, Dept Gen Surg, Dalian, Peoples R China
[2] Dalian Univ Technol, Cent Hosp, Dept Anorectal Surg, Dalian, Peoples R China
[3] Dalian Med Univ, Inst Coll Integrat Med, Dalian, Peoples R China
[4] Dalian Univ Technol, Dept Cardiovasc Surg, Cent Hosp, Dalian, Peoples R China
[5] Dalian Univ Technol, Cent Hosp, Dept Urol, Dalian, Peoples R China
[6] Dalian Med Univ, Hosp 2, Dept Tradit Chinese Med, Dalian, Peoples R China
基金
中国国家自然科学基金;
关键词
Severe acute pancreatitis; Acute lung injury; Emodin; miR-217-5p; Sirt1; APOPTOSIS; MIR-217; CELL; INFLAMMATION; FAMILY;
D O I
10.1016/j.jphs.2024.08.007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Acute lung injury (ALI) is closely related to high mortality in severe acute pancreatitis (SAP). This study unveils the therapeutic effect and mechanism of miR-217-5p on SAP-associated ALI. The miR-217-5p RNA expression was significantly up-regulated in lipopolysaccharide (LPS)-stimulated primary rat alveolar epithelial type II cells (AEC II) and sodium taurocholate-treated pancreas and lung in SAP rats. miR-217 inhibition protected AEC II from LPS-induced damage by inhibiting apoptosis and reducing the TNF-alpha, IL-6, and ROS levels. miR-217 inhibition suppressed apoptosis and alleviated mitochondrial damage through mitochondria-mediated apoptotic pathway in vitro. Sirt1 is a direct target of miR-217-5p. Dual-luciferase reporter assay confirmed the binding of miR-217-5p to Sirt1 mRNA 3 '-UTR. The rescue experiment identified that the anti-apoptotic, anti-inflammatory, and anti-oxidative effects of miR-217 inhibition were mediated by Sirt1 in vitro. Emodin (EMO) protected AEC II from LPS-induced damage and alleviated pancreatic and lung tissue injuries. EMO exerted similar effects as miR-217 inhibition in vitro and in vivo. The effects of EMO were abolished by miR-217 overexpression. In conclusion, miR-217-5p inhibition exerts protective effects on SAP-ALI in vitro and in vivo by repressing apoptosis, inflammation, and oxidative stress through Sirt1 activation. EMO protects against lung injuries in SAP-associated ALI rats through miR-217-5p/Sirt1 axis.
引用
收藏
页码:188 / 197
页数:10
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