Date of Award
Basic Biomedical Science
Dr. Yi-Fan Li
Dr. Curtis Kost
Dr. Hong Zheng
Ischemia-reperfusion, Preconditioning, Carvedilol, Sexual Dimorphism, Murine
Biological Phenomena, Cell Phenomena, and Immunity
Many studies have been done on ischemic preconditioning and its protective effects using the murine model with overwhelmingly consistent and promising results. However, many clinical trials have failed to demonstrate the protective effects of ischemic preconditioning. The causes of the inconsistency are unknown. The effect of sex on ischemic preconditioning protection is largely unclear, which may be a contributing factor. Additionally, in clinical trials, the recruited patients were most likely taking some medications. This project aimed to test the differences in sex on preconditioning protection and the effect of a common β-blocker medication, Carvedilol, on preconditioning protection. Tourniquet-induced unilateral hindlimb ischemia-reperfusion in mice was used as the model. Blood flow in hindlimb paws was measured. Related cytokines were examined using Western blots, including pro-inflammatory IL-6, MCP-1, and TNFα. Additionally, both the non-canonical and canonical NF-κB pathways were investigated using Western blots. Using immunofluorescence staining, monocyte marker CD11b, pro-inflammatory macrophage marker CD68, and anti-inflammatory macrophage marker CD206 were assessed. Overall, there were differences after hindlimb reperfusion in males and females. The macrophage markers were the most notably different between the preconditioning group and the Carvedilol + preconditioning group, making this an exciting topic for further study.
Miller, Casey JC, "Investigating the Effects of Sex and Carvedilol on Ischemia Preconditioning Protective Effect" (2023). Honors Thesis. 284.