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

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.

Apremilast exerts protective effects on stroke outcomes and blood–brain barrier (BBB) dysfunction through regulating Rho‐associated protein kinase 2 expression

“…Previous studies have suggested that ROCK2 performs functional roles in multiple cellular processes, including cell motility, cell adhesion, cell apoptosis, vascular inflammation, and reconstruction (Noma et al., 2006 ). In addition, ROCK2 expression is subject to changes under pathophysiological conditions (Magro et al., 2020 ; Qin et al., 2022 ; Zhou et al., 2020 ). It has been reported that ROCK2 is connected to diverse cardiovascular diseases, including atherosclerosis, hypertension, cardiac hypertrophy, and ischemic stroke (Lee et al., 2014 ; Okamoto et al., 2013 ; Takeda et al., 2019 ; Yamamura et al., 2021 ).…”

Extracellular Vesicle-Encapsulated miR-183-5p from Rhynchophylline-Treated H9c2 Cells Protect against Methamphetamine-Induced Dependence in Mouse Brain by Targeting NRG1

“…It can be exemplified with the study on EVs-encapsulated miR-29, which has been showed to regulate morphine-mediated neuronal dysfunction by targeting platelet-derived growth factor-B [22]. Moreover, our previous study showed the expressions of some miRNAs were changed in heart in Meth-induced rats, whereas these miRNAs can be reversed by Rhy treatment [23]. It is thus essential to study the roles and mechanisms of action of cardiomyocyte-derived EVs-containing miRNA in Meth dependence and Rhy treatments.…”

Nrf2 attenuates methamphetamine-induced myocardial injury by regulating oxidative stress and apoptosis in mice

“…11 MA can also induce Rho-associated protein kinase 2 (ROCK2), which plays an important role in regulating apoptosis of myocardial cells. [12][13][14] To date, however, the mechanism by which MA induces oxidative stress and apoptosis is not clear in the field of drug injury, and further research is needed.…”