Zhou Xing, Tang Xue, Wu Xia, Li Bo-Nan, Zhou Hai-Liang, Hu Hai-Lin, Ning Gang
Department of Andrology, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410007, China.
Department of Andrology, General Hospital of Eastern Theater Command, Nanjing, Jiangsu 21002, China.
Zhonghua Nan Ke Xue. 2020 Dec;26(12):1129-1134.
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).
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.
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).
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.
探讨雄蚕益肾方(XP)介导的PINK1和Parkin信号通路对迟发性性腺功能减退(LOH)雄性大鼠睾丸间质细胞线粒体自噬的影响。
将20只18月龄雄性SD大鼠随机分为LOH模型对照组、低剂量XP组、中剂量XP组和高剂量XP组,另取5只2月龄雄性SD大鼠作为正常对照组。低、中、高剂量XP组大鼠分别按10.4、20.8和41.6 g/kg灌胃给予XP颗粒,正常对照组和LOH模型对照组给予等体积蒸馏水,均连续给药28天。然后取大鼠睾丸组织,在电子显微镜下观察睾丸间质细胞超微结构,并采用蛋白质免疫印迹法检测PINK1、Parkin和p62蛋白的表达。
正常对照组睾丸间质细胞线粒体形态基本正常,自噬明显;模型对照组自噬较少;XP干预组均表现出自噬。与正常对照组相比,LOH模型组睾丸组织中PINK1和Parkin蛋白表达明显降低,p62蛋白表达明显升高(P < 0.05)。与模型对照组相比,低、中、高剂量XP组大鼠睾丸组织中PINK1蛋白表达显著升高,中、高剂量组Parkin蛋白表达显著升高(P < 0.05),而三个XP组p62蛋白表达均显著下调(P < 0.05)。
雄蚕益肾方可增强LOH大鼠睾丸间质细胞降低的线粒体自噬,这可能与其上调PINK1和Parkin表达、下调p62表达以及对睾丸间质细胞超微结构的影响有关。