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Pharmacology. 2019 Dec 11:1-11. doi: 10.1159/000503756. [Epub ahead of print]

Expression of miR-133a-5p and ROCK2 in Heart in Methamphetamine-Induced Rats and Intervention of Rhynchophylline.

Author information

1
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
2
Central Laboratory, Southern Medical University, Guangzhou, China.
3
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China, 1021336808@qq.com.

Abstract

INTRODUCTION:

Rhynchophylline, as a traditional Chinese medicine, was used for the treatment of drug addiction.

OBJECTIVE:

To investigate miRNAs expression profile in the rat hearts of methamphetamine dependence and the intervention mechanisms of rhynchophylline.

MATERIALS AND METHODS:

This study detected the expression profile of miRNAs in the methamphetamine-induced rat hearts by microarray and verified the expression of miR-133a-5P and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) protein.

RESULTS:

After conditioned place preference training, methamphetamine significantly increased the time spent in the drug-paired compartment, while rhynchophylline and MK-801 could reduce the time. Cluster analysis results of miRNAs showed that compared with the control group, the expression of miR-133a-5p in methamphetamine-induced rat hearts was decreased significantly; rhynchophylline could significantly increase the expression of miR-133a-5p. The result was verified by real-time polymerase chain reaction. The results of target gene predictive software and related research showed that ROCK2 protein may be the target gene of miR-133a-5p. The immunohistochemistry results of heart tissues showed that the expression of ROCK2 protein was significantly upregulated in the methamphetamine group and downregulate in the rhynchophylline group; the difference between the MK-801 group and the methamphetamine group was not significant. The result of western blot was consistent with the immunohistochemistry.

CONCLUSION:

The active ingredient of Chinese herbal medicine rhynchophylline can effectively inhibit the formation of methamphetamine-dependent conditional place preference (CPP) effect in rats to some extent. MiR-133a-5p may participate in the cardioprotective effects of CPP rats by targeting ROCK2.

KEYWORDS:

Conditioned place preference; Methamphetamine; ROCK2; Rhynchophylline; miR-133a-5p

PMID:
31825931
DOI:
10.1159/000503756

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