摘要
In the present study,we studied the effects of 3,4-dihydroxybenzaldehyde,derived from Salvia miltiorrhiza Bunge,on mouse sperm survival and sperm membrane integrity in vitro and on mouse reproductive damage induced by cyclophosphamide in vivo.3,4-Dihydroxybenzaldehyde(0.01,0.1,and 1 mg/m L)improved sperm survival rate and sperm membrane integrity in separated mouse sperm(all P<0.05).In cyclophosphamide-treated male mice(60 mg/kg/d through intraperitoneal injection for 5 d),3,4-dihydroxybenzaldehyde(40 mg/kg/d through intragastric gavage for 35 d)increased the testis index,epididymis index,and sperm nuclear maturity(all P<0.05).3,4-Dihydroxybenzaldehyde also improved testis morphology characterized by orderly arranged layers of spermatogenic cells,numbers of sperm in the lumen,normal mesenchymal cells,and close and tidy arrangement of the seminiferous tubules.3,4-Dihydroxybenzaldehyde also increased testicular superoxide dismutase activity and elevated DJ-1 expression.In addition,it decreased the expression of ICAM-1 and enhanced the expressions of VCAM-1,PEDF,VEGF,and PPARγ.These findings indicated that 3,4-dihydroxybenzaldehyde increased mouse sperm survival and sperm membrane integrity in vitro and reduced mouse reproductive damage induced by cyclophosphamide via DJ-1 and other targets in vivo.3,4-Dihydroxybenzaldehyde might thus be useful for treating male reproductive damage and antineoplastic cyclophosphamide-induced reproductive toxicity.
我们研究了来自丹参的3,4-二羟基苯甲醛对体外小鼠精子存活和精子细胞膜完整性的影响,以及对环磷酰胺在体内诱导的小鼠生殖损伤的影响。3,4-二羟基苯甲醛(0.01,0.1和1 mg/mL)可提高分离的小鼠精子存活率和精子细胞膜完整性(均P<0.05)。在环磷酰胺处理的雄性小鼠(腹腔注射60 mg/kg/d,共5天)中,3,4-二羟基苯甲醛(灌胃40 mg/kg/d,共35天)增加睾丸指数、附睾指数和精子核成熟度(均P<0.05)。3,4-二羟基苯甲醛还改善了睾丸形态,其特征是生精细胞层排列有序,腔内精子数量增多,间质细胞正常,生精小管排列紧密。3,4-二羟基苯甲醛还增加了睾丸超氧化物歧化酶(SOD)活性并提高了DJ-1表达。此外,它还降低了ICAM-1的表达并增加了VCAM-1、PEDF、VEGF和PPARγ的表达。这些结果表明,3,4-二羟基苯甲醛在体外可增加小鼠精子存活率和精子细胞膜完整性,并在体内通过DJ-1和其他靶点减少环磷酰胺对小鼠睾丸的损伤。因此,3,4-二羟基苯甲醛可用于治疗男性生殖损伤和抗肿瘤药环磷酰胺引起的生殖毒性。
基金
Science and Technology Program of the Beijing Municipal Education Commission(Grant No.KM201810025002)
National Natural Science Foundation of China(Grant No.81801522)
Natural Science Foundation of Hebei Province(Grant No.H2018209342)。