Objective: To investigate the effects of PINK1 and Parkin pathways mediated by Xiongcanyishen Prescription (XP) on the mitochondrial autophagy of Leydig cells in male rats with late-onset hypogonadism (LOH).
Methods: Twenty 18-month-old male SD rats were randomly divided into an LOH model control, a low-dose XP, a medium-dose XP and a high-dose XP group, and another 5 two-month-old male SD rats were included as normal controls. The animals in the low-, medium- and high-dose XP groups were treated intragastrically with XP granules at 10.4, 20.8 and 41.6 g/kg, while the normal and LOH model controls with the same volume of distilled water, all for 28 successive days. Then the testis tissues of the rats were harvested for observation of the ultrastructure of the Leydig cells under the electron microscope, and the expressions of PINK1, Parkin and p62 proteins were detected by Western blot.
Results: The mitochondria in the Leydig cells of the normal controls were basically normal in morphology, with evident autophagy, those of the model controls showed less autophagy, and those in the XP intervention groups all exhibited autophagy. The expressions of PINK1 and Parkin proteins in the testis tissue were significantly lower and that of p62 markedly higher in the LOH model than in the normal controls (P < 0.05). Compared with the rats in the model control group, those treated with XP showed remarkable elevation in the expression of PINK1 in the low-, medium- and high-dose groups and that of Parkin in the medium- and high-dose groups (P < 0.05), but a significantly down-regulated expression of p62 in all the three XP groups (P < 0.05).
Conclusions: Xiongcanyishen Prescription can enhance the decreased mitochondrial autophagy of Leydig cells in LOH rats, which may be related to its ability of up-regulating the expressions of PINK1 and Parkin and down-regulating that of p62 and its influence on the ultrastructure of Leydig cells.
Keywords: Leydig cell; PINK1; Parkin; late-onset hypogonadism; mitochondrial autophagy; Xiongcanyishen Prescription.