AIM To investigate the effects of CD38 inhibitors on myocardial ischemia reperfusion injury.
METHODS Twenty male Sprague-Dawley rats were given adaptive feeding for 7 days and they were randomly divided into four groups: A. Sham group, B. Myocardial ischemia/reperfusion (I/R) group, C. Myocardial ischemia/reperfusion + CD38 inhibitor group and D. Myocardial ischemia/reperfusion + CD38 inhibitor + Sirt3 inhibitor (3-TYP) group. Myocardial I/R model was established in groups B, C and D. CD38 inhibior Luteolin 100 mg/(kg/d) was administered by gavage for 2 weeks in C and D groups, and 3-TYP was injected via tail vein 30min before modeling in D group. Electrocardiogram (ECG), serum troponin T (cTNT) level, ROS level, myocardial lesion and the expressions of Sirt3, FoxO1, Bax and Bcl-2 in myocardial tissue were detected.
RESULTS The ECG ST segment elevation in group B was significantly higher than that in group A, ST segment in group C was lower than that in group B and ST segment in group D was higher than that in group C. The troponin T and ROS levels in group B were obvious higher than those in group A (P<0.01), the troponin T and ROS levels in group C were significant lower than those in group B (P<0.01) and the troponin T and ROS levels in group D were higher than those in group C (P<0.01 and P<0.05). HE staining showed that the myocardium in group A was arranged neatly and there was no obvious inflammatory infiltration. The structure of group B was disordered and inflammatory cells infiltration was observed. The structures of group C and group D were more orderly than that of group B. TUNEL staining showed that the proportion of TUNEL positive cells in group B was markedly greater than those in group A and group C (P<0.01), and the proportion in group C was much less than that in group D (P<0.01). The protein expression level of Sirt3 in group B was significant lower than those in groups A, C and D (P<0.01) and the expression level in group C was obviously greater than that in group D (P<0.05). The expressions of FoxO1 protein and Bcl-2 protein in group B were much less than those in group A and group C (both, P<0.01), and the expressions in group C was obviously higher than those in group D (P<0.01 and P<0.05). However, the expression of Bax protein in group B was notably higher than those in group A and group C (both, P<0.01), and the expression in group C was prominently lower than that in Group D (P<0.01).
CONCLUSION CD38 inhibitor inhibits myocardial I/R injury through Sirt3/FoxO1 pathway.
DownLoad: