Emodin Ameliorates Severe Acute Pancreatitis-Associated Acute Lung Injury in Rats by Modulating Exosome-Specific miRNA Expression Profiles

被引：9
|
作者：
Yang, Qi [1 ,2 ,3 ,4 ]
Luo, Yalan [1 ,2 ,3 ]
Ge, Peng [1 ,2 ,3 ]
Lan, Bowen [1 ,2 ,3 ]
Liu, Jin [1 ,2 ,3 ]
Wen, Haiyun [1 ,2 ,3 ]
Cao, Yinan [1 ,2 ,3 ]
Sun, Zhenxuan [1 ,2 ,3 ]
Zhang, Guixin [1 ,2 ,3 ]
Yuan, Huiming [5 ]
Zhang, Lihua [5 ]
Chen, Hailong [1 ,2 ,3 ]
机构：
[1] Dalian Med Univ, Affiliated Hosp 1, Dept Gen Surg, Dalian 116011, Liaoning, Peoples R China
[2] Dalian Med Univ, Inst Coll Integrat Med, Dalian 116011, Liaoning, Peoples R China
[3] Dalian Med Univ, Affiliated Hosp 1, Lab Integrat Med, Dalian 116011, Liaoning, Peoples R China
[4] Dalian Med Univ, Affiliated Hosp 2, Dept Tradit Chinese Med, Dalian 116023, Peoples R China
[5] Chinese Acad Sci, Natl Chromatog Res & Anal Ctr, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
来源：
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2023年 / 18卷
基金：
国家重点研发计划; 中国国家自然科学基金;
关键词：
severe acute pancreatitis; acute lung injury; emodin; exosome; microRNA; MYOCARDIAL INJURY; MACROPHAGES; PROTECTS;
D O I：
10.2147/IJN.S428924
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
Background: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear. Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO. Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats. Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO.
引用
收藏
页码：6743 / 6761
页数：19
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