Rats were randomly assigned into seven groups and pre-treatment on a daily basis for 7 days before ligating the left anterior descending coronary artery to induce MI. Echocardiographic indexes were recorded to determine cardiac function. TTC staining was performed to determine infarct size. Plasma enzymes involved antioxidantion and hydrogen sulfide levels also were determined. Western blot analysis was used to reveal the expression of proteins relate to anti-inflammation and CSE/H2S pathway. Mixed-mode reversed-phase and cation-exchange HPLC–MS/MS method was used to study the pharmacokinetic properties of CR-SPRC and SPRC in MI models rat.
Compared to MI group CR-SPRC remarkable decreased infarct size (P < 0.01), mortality (P < 0.05), CK (P < 0.05), LDH (P < 0.01), MDA (P < 0.01) levels and increased CAT (P < 0.05), GSH (P < 0.01), SOD (P < 0.01), H2S (1.8-fold, P < 0.01) levels. Echocardiographic show that CR-SPRC notably increased EF (P < 0.01), FS (P < 0.01), LVAWs (P < 0.01) and decreased LVIDs (P < 0.01), LVIDd (P < 0.01), LVs (P < 0.01), LVd (P < 0.01). When compared to SPRC group CR-SPRC was also markedly lower CK (P < 0.05), MDA (P < 0.01), and higher H2S level (1.3-fold P < 0.01) meanwhile increased EF (P < 0.01), FS (P < 0.01), LVAWs (P < 0.05) and decreased LVIDs (P < 0.01), LVs (P < 0.05), LVd (P < 0.01). Noteworthy when compared to Captoril CR-SPRC significantly reduced infarct size (P < 0.01), mortality (P < 0.05), increased EF(P < 0.01), FS (P < 0.01), LVAWs (P < 0.01) and decreased LVIDs (P < 0.01), LVIDd (P < 0.01), LVs (P < 0.05), LVd (P < 0.01). Inflammatory biomarkers at protein levels (P-P65/P65,TNF-伪) were markedly higher in MI than CR-SPRC (P < 0.05) when CSE, Ik-Ba protein levels were markedly lower in MI than CR-SPRC (P < 0.01 and P < 0.05 respectively). All these effects of CR-SPRC and SPRC were abolished in addition of Propagylglycine (PAG, a CSE inhibitor). CR-SPRC also has better pharmacokinetic properties than SPRC by reduce the concentration peak (Cmax),delay time to reach peak concentration (Tmax), prolong the mean residence time (MRTinf) and improve bioavailability.
All evidence from this study demonstrated the cardioprotective effects and improve cardiac function of CR-SPRC on MI model by anti-inflammation, anti-oxidantion and modulated CSE/H2S pathway. More importantly, CR-SPRC showed better effects than normal SPRC and Captoril. These results was attributed to favourable pharmacokinetic properties of CR-SPRC.