MiR-22 inhibits myocardial fibrosis in rats with myocardial infarction by targeting PTEN/Akt/mTOR signaling pathway.

This study aimed to evaluate the effects of miR-22 on myocardial fibrosis in rats with myocardial infarction (MI) and to further explore the possible underlying mechanism. A total of 80 rats were randomly divided into Sham group, miR-22 overexpression group, MI group or MI + miR-22 overexpression group. Reverse transcription-polymerase chain reaction (RT-PCR) results showed that compared with Sham group, miR-22 expression level in myocardial tissues of rats decreased significantly in MI group. Overexpression of miR-22 could remarkably relieve cardiac insufficiency in MI rats, increase EF% and FS%, and reduce collagen deposition and the mRNA expression level of fibrosis-promoting genes in myocardial tissues of MI rats. The cross-sectional area of myocardial cells in MI + miR-22 mimic group was smaller than that in MI group. According to the results of immunohistochemical staining, overexpression of miR-22 notably reduced the level of oxidative stress marker 4-HNE in myocardial tissues of MI rats. Meanwhile, myocardial cells in MI + miR-22 mimic group exhibited a prominently lower apoptosis rate than those in MI group. Furthermore, Western blotting results demonstrated that overexpression of miR-22 inhibited the activation of the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt/mTOR signaling pathway in myocardial tissues of MI rats. The inhibitory effects of miR-22 on myocardial fibrosis and hypertrophy after MI in rats may be related to its inhibition on the PTEN/Akt/mTOR signaling pathway. All our findings suggested that miR-22 is expected to become a targeted drug for the clinical treatment of MI.

[Apoptosis of melanoma B16 cells induced by gambogenic acid].

OBJECTIVE: To study the inhibitory effect of Gambogenic acid (GNA) on melanoma B16 cells proliferation, and to explore the role of cell apoptosis. METHODS: The inhibitory effect of GNA on the proliferation of B16 cells was measured by methyl thiazolyl tetrazolium (MTT) assay; Alternation of B16 cells ultrastructure was detected by AO/EB staining under fluorescent microscope; Flow cytometry was used to detect intracellular reactive oxygen species (ROS) in B16 cells generated by GNA treatment Western blotting was used to investigate the expression of intracellular Caspase-3 proteins changes. RESULTS: MTT results showed that the GNA within a certain time and a certain concentration significantly suppressed the proliferation of B16 cells and morphological changes were observed by fluorescence microscope on B16 cells after GNA treatment. AO/EB staining showed that the major cell density decreased. GNA treated cells showed obvious apoptotic status. After the cells treated with GNA, in a short period of time, intracellular ROS levels increased dramatically compared with the control group (P < 0.01), and the mitochondrial membrane had a low potential consistently. Western blotting results showed that changes of intracellular proteins expression in the release of Caspase-3 proteins expression levels were increased after GNA treatment. CONCLUSION: GNA can inhibit malignant melanoma B16 cells growth and proliferation and induce apoptosis within a certain time and at a certain concentration.