The protective effect of low-energy shock wave on testicular ischemia-reperfusion injury is mediated by the PI3K/AKT/NRF2 pathway.

Aims: Testicular ischemia-reperfusion (IR) injury is the primary pathophysiological consequence of testicular torsion. Low-energy shock wave (LESW) is an effective treatment for certain diseases. The present study investigated whether LESW could improve on testicular IR injury in rats and examined the involved mechanism.

Main Methods: Testicular reperfusion was induced in rats after 1-h ischemia. The first LESW treatment was performed 30 min prior to testicular reperfusion, and then every other day for another 3 applications. LY294002 was applied to investigate the involved mechanism. Testicular morphological changes and malonaldehyde (MDA) level were respectively assessed by hematoxylin-eosin staining. Western blot and thiobarbituric acid method. Western blot, real-time quantitative PCR and immunohistochemistry were performed to assess the apoptosis, the activation of phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) pathway the nuclear factor erythroid 2-related factor 2 (NRF2) and vascular endothelial growth factor A (VEGF-A) level in the testis of rats.

Key Findings: LESW improved testicular IR injury in rats. Moreover, LESW upregulated the phosphorylation levels of AKT and glycogen synthase kinase 3β (GSK-3β). Also, it upregulated the levels of nuclear NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO-1) in these rats. Nevertheless, LY294002 blocked these protective effects. LESW also upregulated VEGF-A level in rats with testicular IR injury.

Significance: This study demonstrated that LESW could ameliorate testicular IR injury in rats, which might be attributed to the activation of PI3K/AKT/NRF2 pathway. These findings suggested the potential of LESW in the treatment of testicular torsion.