Dexmedetomidine Leads to the Mitigation of Myocardial Ischemia/Reperfusion-Induced Acute Lung Injury in Diabetic Rats Via Modulation of Hypoxia-Inducible Factor-1α.

Abstract

INTRODUCTION:

The objective of this study is to investigate the protective mechanism of dexmedetomidine (Dex) in myocardial ischemia/reperfusion (MIR)-induced acute lung injury (ALI) of diabetic rats by inhibiting hypoxia-inducible factor-1α (HIF-1α).

METHODS:

Initially, healthy male Sprague Dawley rats were treated with streptozocin to induce diabetes. Then, three weeks after the induction, Dex or lentiviral vector (LV)-HIF-1α was injected into the rats 30 minutes prior to the MIR modeling. After four weeks, lung tissues were harvested for pathological changes observation and the wet/dry weight (W/D) ratio determination. Afterwards, oxidative stress indicators and pro-inflammatory factors were measured. In addition, HIF-1α expression was assessed by immunohistochemistry and western blot analysis.

RESULTS:

Dex could suppress inflammatory cell infiltration, improve lung tissue structure, reduce pathological score and the W/D ratio, and block oxidative stress and inflammatory response in MIR-induced ALI of diabetic rats. Besides, Dex could also inhibit HIF-1α expression. Moreover, Dex + LV-HIF-1α reversed the protective role of Dex on diabetic MIR-induced ALI.

CONCLUSION:

Our study has made it clear that Dex inhibited the upregulation of HIF-1α in diabetic MIR-induced ALI, and thus protect lung functions by quenching the accumulation of oxygen radical and reducing lung inflammatory response.

• Authors: Siyu Chen, Jianjiang Wu, Long Yang, Taiwangu Tailaiti, Tiantian Zou, Yidan Huan, Jiang Wang
• Journal: Brazilian journal of cardiovascular surgery (Braz J Cardiovasc Surg) Vol. 37 Issue 3 Pg. 370-379 (05 23 2022) ISSN: 1678-9741 [Electronic] Brazil
• PMID: 35605218 (Publication Type: Journal Article)

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• Dexmedetomidine

Topics

• Acute Lung Injury (drug therapy, etiology, prevention & control)
• Animals
• Dexmedetomidine (pharmacology, therapeutic use)
• Diabetes Mellitus, Experimental (complications, pathology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Lung (pathology)
• Male
• Myocardial Reperfusion Injury (pathology, prevention & control)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction