[Regulatory effect of Jinkui Shenqi Pills on the gene expression of the Nrf2 signaling pathway in cyclophosphamide-induced testis injury in mice].

OBJECTIVE: To investigate the protective effect of Jinkui Shenqi Pills (JSP) against cyclophosphamide-induced testis injury (TI) and its anti-oxidation mechanism in mice. METHODS: Thirty male mice were equally divided into a blank control, a TI model control and a JSP treatment group. The mice in the JSP treatment group were treated intragastrically with JSP and the blank controls with normal saline at 1.2 g/kg qd for 7 days, and then the animals in both the TI model control and JSP treatment groups were injected intraperitoneally with cyclophosphamide at 50 mg/kg, once a week, for 35 days, to induce testis injury. After modeling, all the mice were weighed and sacrificed, followed by detection of the serum T content, measurement of the testis weight, examination of semen parameters in the caudad epididymis, and determination of the levels of super oxide dismutase (SOD) and malondialdehyde (MDA) in the testis tissue and the expressions of relevant genes by qRT-PCR. RESULTS: The mice of the TI model control group, compared with the blank controls, showed significant decreases in the body weight (ï¼»34.63 ± 1.92ï¼½ vs ï¼»48.32 ± 1.64ï¼½ g, P<0.05), testis weight (ï¼»80.00 ± 3.90ï¼½ vs ï¼»140.00 ± 6.10ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.22 ± 0.01ï¼½ vs ï¼»0.31 ±0.03ï¼½%, P<0.05), sperm motility (ï¼»48.66 ± 8.08ï¼½% vs ï¼»89.33 ± 4.04ï¼½%, P<0.05), sperm concentration (ï¼»28.42 ± 5.26ï¼½ vs ï¼»77.67 ± 8.73ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»8.75 ± 0.96ï¼½ vs ï¼»21.75 ± 1.71ï¼½ pg/ml, P<0.05) and SOD (ï¼»140.82 ± 10.08ï¼½ vs ï¼»358.52 ± 40.41ï¼½ U/mg prot, P<0.05), but remarkable increases in the sperm deformity rate (ï¼»37.33 ± 2.08ï¼½ vs ï¼»15.33±1.53ï¼½%, P<0.05) and MDA level (ï¼»54.89±6.09ï¼½ vs ï¼»30.21±2.17ï¼½ nmol/ng prot, P<0.05). The mice of the JSP treatment group, in comparison with the TI model controls, exhibited markedly increased body weight (ï¼»39.80±2.89ï¼½ vs ï¼»34.63±1.92ï¼½g, P<0.05), testis weight (ï¼»130.00 ± 11.00ï¼½ vs ï¼»80.00 ± 3.90ï¼½ mg, P<0.05), testicular organ coefficient (ï¼»0.28 ± 0.01ï¼½ vs ï¼»0.22 ± 0.01ï¼½%, P<0.05), sperm motility (ï¼»76.00 ± 5.29ï¼½% vs ï¼»48.66 ± 8.08ï¼½%, P<0.05), sperm concentration (ï¼»56.08 ± 4.29ï¼½ vs ï¼»28.42 ± 5.26ï¼½ ×106/ml, P<0.05), and levels of serum T (ï¼»15.50 ± 1.29ï¼½ vs ï¼»8.75 ± 0.96ï¼½ pg/ml, P<0.05) and SOD (ï¼»206.59 ± 16.38ï¼½ vs ï¼»140.82 ± 10.08ï¼½ U/mg prot, P<0.05), but decreased sperm deformity rate (ï¼»25.01 ± 2.99ï¼½% vs ï¼»37.33 ± 2.08ï¼½%, P<0.05) and MDA level (ï¼»35.84 ± 3.61ï¼½ vs ï¼»54.89 ± 6.09ï¼½ nmol/ng prot, P<0.05). The mRNA expressions of NOQ-1, Nrf2 and HO-1 in the testis tissue were significantly lower and that of Caspase-3 remarkably higher in the TI model control than in the blank control group (P<0.05), while those of Nrf2 and HO-1 significantly higher and that of Caspase-3 markedly lower in the JSP treatment group than in the TI model controls (P<0.05). Histopathological images displayed reduced layers of spermatogenic cells in the seminiferous tubules, complete exfoliation of the spermatogenic cells in some of the tubules and decreased number of sperm cells in the TI model controls, which were all found normal in the JSP treatment group. CONCLUSIONS: Jinkui Shenqi Pills can effectively inhibit cyclophosphamide-induced testis injury, which may be related to its effect of regulating the gene expression of the Nrf2 signaling pathway and enhancing the activity of antioxidant enzymes.