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Recently, with the development of RNA research techniques, a wide variety of circular RNAs (circRNAs) have been discovered and some of them are confirmed to have crucial biological functions. CircRNAs arise from exons (i.e. exonic circRNAs) or introns (i.e. intronic circRNAs). Acting as microRNA sponges or combining with proteins, circRNAs participate in the regulation of gene expression and influence the activity of some proteins. In addition, some circRNAs even encode proteins. More importantly, several circRNAs play a key role in the occurrence and progression of some tumors, including stomach, liver, colon, breast, cervical, and ovarian cancers. Therefore, circRNAs may be a novel type of diagnostic marker and therapeutic target of cancers.
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BACKGROUND: It is demonstrated in modern pharmacologic study that total paeony glycoside (TPG) provides extensive pharmacologic activities,such as inhibiting aggregation of platelets and erythrocytes, anticoagulation,antithrombsis, anti-arterial sclerosis, protecting heart and liver, anti-tumor,etc.OBJECTIVE: Neonatal rat cardiomyocytes were cultured in vitro and by the changes of superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) contents in cell culture solution, the protection of TPG on injured cardiomyocytes was analyzed.DESIGN: Controlled observation was designed.SETTING: Bioengineering Department in School of Life Science and Technology of Xi 'an Jiaotong University and Institute of Bone Diseases in Medical School of Xi'an Jiaotong University.MATERIALS: The experiment was performed in Bioengineering Department in School of Life Science and Technology of Xi 'an Jiaotong University from February to June in 2003, in which, 44 SD neonatal rats aged 1-3 days were employed. The 48-hour-cultured cardioryocytes were prepared in 42 bottles and randomized into 6 groups, named normal control (normal group), medicated-injury group (injury group), TPG 0.625 mg/L group,TPG 3.125 mg/L group, TPG 15.625 mg/L group and positive control, 7 bottles in each group.METHODS: Cardiomyocytic primary culture was performed under aseptic condition. No any drug was used in normal group, isoprenaline was added in injury group to terminate the concentration at 100 mg/L, in TPG 0.625, 3.125 and 15.625 mg/L groups, 30 minutes after isoprenaline added, RGP at dosages of 0.625, 3.125 and 15.625 mg/L were added respectively; in positive control, 30 minutes after isoprenaline added, coenzyme Q10 was used to terminate the concentration as 100 mg/L.Afterwards, the assay of every index was performed. Xanthine oxidase (XOD) method was used to assay SOD activity, thiobarbituric acid (TBA)method was to assay MDA content and nitrate reductase (NR) method was to assay NO content.cell culture solution in each group.Compared with normal group, the levels of total SOD, CuZn-SOD and MnSOD were reduced remarkably in injury group (P ＜ 0.05 or P ＜ 0.01).The above-indexes in every TPG group and positive control were improved to different extents (P ＜ 0.05 or ＜ 0.01), in which, the protection of TPG 15.625 mg/L group was near to or superior to positive control [(79.50±10.67), (80.30±13.50); (48.24±13.26), (49.73±10.23); (31.26±10.22),in cell culture solution in each group: Those in injury group were higher remarkably than normal group (P ＜ 0.01). MDA and NO contents were all reduced in every TPG group and positive control and dose dependence presented in TPG protection, the higher the dose was, the stronger the action of TPG on protection was, in which, in high-dose group, MDA content was near to normal group [(5.41±1.81), (4.48±0.94) μmol/L, P ＞ 0.05] and NO content was similar to positive control [(81.83± 9.08), (82.41±12.37) mol/L,P ＞ 0.05].CONCLUSION: TPG protects myocardial injury induced by isoprenaline,indicating dose-dependence relationship, which is probably associated with enhanced anti-oxidation of cell, reduced injury of cellular membrane induced by free radical and lipid oxidant.
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Aim To further investigate the protective effect and mechanisms of total paeony glycoside (TPG) on apoptosis in experimental myocardial ischemic rats.Methods The myocardial ischemic model of rats was established by subcutaneous injection of isoprenaline (ISO), and early apoptosis rate of myocardial cells and the expression of apoptosis related genes Bax, Bcl-2 and proteins in myocardial tissues were analyzed and contrasted among five groups, including normal control, ISO injury, TPG prevention and treatment, TPG treatment and positive control.Results Compared with ISO injury group, all of indexes had improved in various degrees in TPG prevention and treatment group and TPG treatment group, such as the decrease of early apoptosis rate,expression of Bax gene and protein, the increase of Bcl-2 gene and protein and the ratio of Bcl-2 protein/Bax protein.Conclusion TPG has protective effect on apoptosis in ischemic myocardium induced by ISO.The pharmacological mechanism may relate to the activation of the Bcl-2 gene and protein expression, the inhibition of Bax gene and protein expression, as well as the increase of Bcl-2/Bax ratio.
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Aim To investigate the antioxidative effect of total paeony glycoside(TPG) on cardiomyocytes injured.Methods The ischemia and hypoxia injuy model of cultured neonatal rat cardiomyocytes was induced by adding isoprenaline(ISO), and superoxide dismutase(SOD), malonalde hyde(MDA) and nitric oxide(NO) in the culture solution of normal control group; ISO injure group, CoQ 10 positive control group as well as protective group s with high,middle or low-dose TPG were respectively analyzed and compared. Results Compared with normal control group,the enzyme activity o f total SOD, CuZn-SOD and Mn-SOD decreased obviously, and the content of MDA and NO increased markedly in injury group, but in TPG and CoQ 10 groups all of detective indicators had improvement in varying degrees, and the protective effect was better than or close to positive control group in high-dose TPG grou p.Conclusion TPG has protective action on injured cardiomyocyte s induced by ISO in dose-dependent manner. The mechanism relates to the enhance ment of antioxidative effect in cells, and the reduction of membrane damage caus ed by free radical and lipid peroxide.