The regulation by immune checkpoint is able to prevent excessive tissue damage caused by ischemia reperfusion (I/R); therefore, the study aims to investigate the behavior of phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) mRNA, miR-1206 and small nucleolar RNA host gene 14 (SNHG14) during I/R and intake of pentoxifylline (PTX) as a protective drug. The relative expression level of PAG1/miR-1206/SNHG14 was determined by qRT-PCR. Cardiac tissue levels of cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and PAG1 protein expression were determined by ELISA technique. The regulatory T cells achieved by the flow cytometry. The results found that the relative expression of SNHG14 was significantly upregulated in I/R, but suppressed in PTX treated groups with enhancement of the relative expression level of miR-1206. The gene and protein expression of PAG1 were downregulated with effective doses of PTX. The results showed that (30 and 40 mg/kg bwt) PTX dose suppressed the CTLA4 development significantly. The mean of the regulatory T cell in PTX protective groups is significantly reduced at (p < 0.001) in a comparison with I/R group. Spearman's correlation analysis revealed a significant negative correlation between SNHG14 and miR-1206, but a significant positive correlation between SNHG14 and PAG1 in I/R heart tissue. The results indicated that miR-1206 and SNHG14 can be used as biomarkers with perfect sensitivity and specificity. Using PTX reduced cardiac tissue damage. SNHG14 and miR-1206 can be used as a diagnostic tool in I/R.
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