[Animal Experiment]-Study on the effect and mechanism of rapamycin on myocardial injury after renal ischemia-reperfusion in rats

  Objective To explore the effects of rapamycin (RAPA) on the cardiac injury of distant organs after renal ischenia reperfusion (RIR) in rats.

  Methods 40 rats were randomly divided into four groups: blank group, sham operation group, RIR group and rapamycin treatment group, with 10 rats in each group. Rats in the rapamycin treatment group received rapamycin gavage. Rats in each group were sacrificed 24 hours after operation, and blood, spleen and heart were collected. The plasma levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum creatinine (SCr) and urea nitrogen (BUN) were measured. Semi-quantitative analysis with PAS staining indicates the degree of cardiac damage. TUNEL kit detects cell apoptosis. Flow cytometry detects the percentage of NKT cells. RT-qPCR method was used to detect the expression of CXC chemokine ligand 10 (CXCL10), hypoxia-inducible factoR-1α (HIF-1α) mRNA and vascular endothelial growth factor (VEGF) mRNA.

  Results The serum BUN and SCr values of the RIR group were higher than those of the sham operation group. The serum CK and CK-MB levels in the rapamycin treatment group were lower than those in the model group. The semi-quantitative score of cardiac damage indicated that the pathological damage score of the rapamycin treatment group was significantly lower than that of the RIR group. The percentage of NKT cells in the heart and peripheral blood of the rapamycin treatment group was significantly higher than that of the RIR group. The percentage of NKT cells in the spleen in the rapamycin treatment group was lower than that in the RIR group. The expression of HIF-1α mRNA and VEGF mRNA in the rapamycin treatment group was lower than that in the RIR group. The expression level of CXCL10 mRNA in the rapamycin treatment group was higher than that in the RIR group.

  Conclusion RAPA can significantly up-regulate the expression level of CXCL10 and promote the accumulation of NKT cells from the spleen to peripheral blood in the heart. RAPA can also inhibit the expression level of HIF-1α to protect the heart after RIR.