【Animal Modeling】-The effect and mechanism of rapamycin on myocardial injury after renal ischemia-reperfusion in rats

  Objective: To investigate the effect of rapamycin (RAPA) on the damage to the heart of distant organs after renal ischemia-reperfusion (RIR) in rats.

  Method: 40 rats were randomly divided into 4 groups: blank group, sham operation group, RIR group, rapamycin treatment group, 10 rats in each group. Rats in the rapamycin treatment group received oral gavage of rapamycin. Rats in each group were sacrificed 24 hours after the operation, and blood, spleen and heart were collected. Measure plasma creatine kinase (CK), creatine kinase isoenzyme (CK-MB), serum creatinine (SCr) and urea nitrogen (BUN) levels. Semi-quantitative analysis with PAS staining indicates the degree of cardiac damage. The TUNEL kit can detect cell apoptosis. Flow cytometry detects the proportion of NKT cells. RT-qPCR was used to detect the expression of CXC chemokine ligand 10 (CXCL10), hypoxia inducible factor 1α (hypoxia inducible factor R-1α, HIF-1α) mRNA and vascular endothelial growth factor (VEGF) mRNA.

  Result: 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 cardiac injury score showed that the pathological injury score of the rapamycin treatment group was significantly lower than that of the RIR group. The proportion of NKT cells in the heart and peripheral blood of the rapamycin treatment group was significantly higher than that of the RIR group. The proportion of NKT cells in the spleen in the rapamycin treatment group was lower than that in the RIR group. The expression levels of HIF-1αmRNA and VEGF mRNA in the rapamycin treatment group were lower than those 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 in the heart from the spleen to the peripheral blood. APA can also block HIF-1α expression levels to protect the heart after RIR.