Abstract
BACKGROUND: Erectile dysfunction (ED), which frequently occurs in individuals with hyperlipidemia, seriously affects quality of life. Lumbrokinase exhibits multiple pharmacological effects. There is currently a lack of evidence to support the use of lumbrokinase in treating ED. We investigated the effect and mechanism of lumbrokinase in a rat model of hyperlipidemia-induced erectile function (HLED). METHODS: There were 28 male Sprague-Dawley rats included. Eight rats received a standard diet as controls; 20 rats were fed a high-cholesterol diet to induce hyperlipidemia. After 8 weeks, the apomorphine test (APO) was used to confirm HLED. Fourteen rats were then allocated into two subgroups: one received lumbrokinase by oral gavage for 4 weeks, and the other received saline as the control group. Erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) measurements. Histopathological and apoptotic changes in the corpus cavernosum were examined, and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) pathway-related protein and gene expression were analyzed using Western blotting and quantitative real-time polymerase chain reaction (RT-qPCR). RESULTS: ICP/MAP were significantly higher in the treatment group than in the model group. Abnormal lipid levels, imbalance between NO and ET-1 and multi-organ lesions observed in the model group were improved in the treatment group. Moreover, the model group showed a higher rate of apoptotic cells, which was also inhibited by the lumbrokinase treatment. Furthermore, lumbrokinase significantly upregulated the expression of Bcl-2, PI3K and Akt and downregulated the expression of cleaved Caspase-3. CONCLUSIONS: Lumbrokinase improved erectile function in rats with HLED, likely by inhibiting apoptosis. These findings provide evidence of a potential treatment option for HLED.