Tetrandrine Ameliorates Myocardial Ischemia Reperfusion Injury through miR-202-5p/TRPV2.

Abstract

OBJECTIVE:

This study is aimed at investigating the therapeutic effects of tetrandrine (Tet) on myocardial ischemia reperfusion (I/R) injury and probe into underlying molecular mechanism.

METHODS:

H9C2 cells were divided into hypoxia/oxygenation (H/R) group, H/R+Tet group, H/R+Tet+negative control (NC) group, and H/R+Tet+miR-202-5p inhibitor group. RT-qPCR was utilized to monitor miR-202-5p and TRPV2 expression, and TRPV2 protein expression was detected via western blot and immunohistochemistry in H9C2 cells. Cardiomyocyte apoptosis was evaluated through detection of apoptosis-related markers and flow cytometry. Furthermore, myocardial enzyme levels were detected by ELISA. Rats were randomly separated into sham operation group, I/R group, I/R+Tet group (50 mg/kg), I/R+Tet+NC group, and I/R+Tet+miR-202-5p inhibitor group. miR-202-5p and TRPV2 mRNA expression was assessed by RT-qPCR. TRPV2 protein expression was detected through western blot and immunohistochemistry in myocardial tissues. Apoptotic levels were assessed via apoptosis-related proteins and TUNEL. Pathological changes were observed by H&E staining. Myocardial infarction size was examined by Evans blue-TCC staining.

RESULTS:

Abnormally expressed miR-202-5p as well as TRPV2 was found in H/R H9C2 cells and myocardial tissues of I/R rats, which was ameliorated following Tet treatment. Tet treatment significantly suppressed H/R- or I/R-induced cardiomyocyte apoptosis. ELISA results showed that CK-MB and LDH levels were lowered by Tet treatment in H/R H9C2 cells and serum of I/R rats. H&E staining indicated that Tet reduced myocardial injury in I/R rats. Also, myocardial infarction size was lowered by Tet treatment. The treatment effects of Tet were altered following cotreatment with miR-202-5p inhibitor.

CONCLUSION:

Our findings revealed that Tet may ameliorate myocardial I/R damage via targeting the miR-202-5p/TRPV2 axis.

• Authors: Wei Zhao, Youyang Wu, Fanhao Ye, Shiwei Huang, Hao Chen, Rui Zhou, Wenbing Jiang
• Journal: BioMed research international (Biomed Res Int) Vol. 2021 Pg. 8870674 ( 2021) ISSN: 2314-6141 [Electronic] United States
• PMID: 33763489 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Wei Zhao et al.

Chemical References

• Benzylisoquinolines
• MicroRNAs
• TRPV Cation Channels
• Trpv2 protein, rat
• tetrandrine

Topics

• Animals
• Benzylisoquinolines (pharmacology)
• Cell Line
• Gene Expression Regulation (drug effects)
• Male
• MicroRNAs (biosynthesis)
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• TRPV Cation Channels (biosynthesis)