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Title: [Regulatory effect of Jinkui Shenqi Pills on the gene expression of the Nrf2 signaling pathway in cyclophosphamide-induced testis injury in mice].
Author: Jiang P, Xu QH, Chen CW, Xia LB, Huang RS, She DY, Liu G, Yan H, Zhong ZM, Bao LL, Zuo RH.
Journal: Zhonghua Nan Ke Xue; 2020 Feb; 26(2):160-166. PubMed ID: 33346421.
Abstract:
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 (［34.63 ± 1.92］ vs ［48.32 ± 1.64］ g, P<0.05), testis weight (［80.00 ± 3.90］ vs ［140.00 ± 6.10］ mg, P<0.05), testicular organ coefficient (［0.22 ± 0.01］ vs ［0.31 ±0.03］%, P<0.05), sperm motility (［48.66 ± 8.08］% vs ［89.33 ± 4.04］%, P<0.05), sperm concentration (［28.42 ± 5.26］ vs ［77.67 ± 8.73］ ×10⁶/ml, P<0.05), and levels of serum T (［8.75 ± 0.96］ vs ［21.75 ± 1.71］ pg/ml, P<0.05) and SOD (［140.82 ± 10.08］ vs ［358.52 ± 40.41］ U/mg prot, P<0.05), but remarkable increases in the sperm deformity rate (［37.33 ± 2.08］ vs ［15.33±1.53］%, P<0.05) and MDA level (［54.89±6.09］ vs ［30.21±2.17］ 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 (［39.80±2.89］ vs ［34.63±1.92］g, P<0.05), testis weight (［130.00 ± 11.00］ vs ［80.00 ± 3.90］ mg, P<0.05), testicular organ coefficient (［0.28 ± 0.01］ vs ［0.22 ± 0.01］%, P<0.05), sperm motility (［76.00 ± 5.29］% vs ［48.66 ± 8.08］%, P<0.05), sperm concentration (［56.08 ± 4.29］ vs ［28.42 ± 5.26］ ×10⁶/ml, P<0.05), and levels of serum T (［15.50 ± 1.29］ vs ［8.75 ± 0.96］ pg/ml, P<0.05) and SOD (［206.59 ± 16.38］ vs ［140.82 ± 10.08］ U/mg prot, P<0.05), but decreased sperm deformity rate (［25.01 ± 2.99］% vs ［37.33 ± 2.08］%, P<0.05) and MDA level (［35.84 ± 3.61］ vs ［54.89 ± 6.09］ 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.

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