黄河包头段水源水有机提取物对雄性小鼠的生殖毒性

Reproductive toxicity of organic extract from source water of Baotou section of the Yellow River to male mice

目的探讨黄河包头段水源水有机提取物对雄性小鼠生殖功能的影响。方法将50只健康SPF级雄性ICR小鼠随机分为对照(玉米油)组和低(12.5 L/kg)、中(25 L/kg)、高剂量(50 L/kg)有机提取物染毒组及黄河水高剂量有机提取物(50 L/kg)+NAC(100 mg/kg)处理组,每组10只。有机提取物采用经口灌胃方式进行染毒;染毒前1 h,黄河水高剂量有机提取物+NAC处理组经腹腔注射染毒NAC溶液;隔日1次,连续4周。检测小鼠精子数量、畸形率和睾丸组织超氧化物歧化酶(SOD)、丙二醛(MDA)、3-硝基酪氨酸(3-NT)水平以及血清8-羟基脱氧鸟苷(8-OhdG)水平。结果与对照组相比,高剂量有机提取物染毒组小鼠的精子数量较低,而中、高剂量有机提取物染毒组和高剂量有机提取物+NAC处理组小鼠的精子畸形率均较高,差异均有统计学意义(P<0.05),且随着有机提取物染毒剂量的升高,小鼠的精子数量呈下降趋势,而精子畸形率呈上升趋势;与高剂量有机提取物染毒组相比,高剂量有机提取物+NAC处理组小鼠的精子数量较高,而精子畸形率较低,差异均有统计学意义(P<0.05)。与对照组相比,各剂量有机提取物染毒组和高剂量有机提取物+NAC处理组小鼠睾丸曲精管中初级精母细胞的数量均降低,差异有统计学意义(P<0.05);且随着有机提取物染毒剂量的增高,小鼠睾丸曲精管中初级精母细胞的数量呈下降趋势;而小鼠睾丸曲精管中精原细胞的数量均无明显变化;与高剂量有机体取物染毒组相比,高剂量有机物提取物+NAC处理组小鼠睾丸曲精管中初级精母细胞的数量增多,差异有统计学意义(P<0.05)。与对照组相比,高剂量有机提取物染毒组和高剂量有机提取物+NAC处理组小鼠血清8-OhdG水平均较高,各剂量有机提取物染毒组和高剂量有机提取物+NAC处理组小鼠睾丸组织3-NT水平也均较高,差异均有统计学意义(P<0.05);而各剂量有机提取物染毒组睾丸组织SOD、MDA水平均无明显改变;且随着有机提取物染毒剂量的升高,小鼠睾丸组织SOD、MDA、3-NT与血清8-OhdG水平均呈上升趋势;与高剂量有机提取物染毒组相比,高剂量有机提取物+NAC处理组小鼠睾丸组织SOD、MDA、3-NT与血清8-OhdG水平均较低,差异均有统计学意义(P<0.05)。结论黄河水中的有机提取物能够对雄性小鼠生殖功能产生影响,氧化损伤和DNA损伤可能是其作用机制。

Objective To understand the effects of organic extracts from source water of Baotou reach of the Yellow River on the reproductive function of male mice. Methods Fifty healthy male ICR mice of SPF grade were randomly divided into five groups,low dose group(12.5 L/kg),moderate dose group(25 L/kg),high dose group(50 L/kg),high dose(50 L/kg) group+100 mg/kg N-acetylcysteic acid(NAC) treatment group and control group,10 rats in each group. The organic extract was given through gavage,once every other day for four weeks,and the exposure value was 20 ml/kg. The rats of high dose +NAC treatment group were intraperitoneally injected with 100 mg/kg NAC one hour before the exposure to organic extracts.The blood,bilateral testes and epididymis were collected for the examination of the pathomorphological changes of testicular tissue,measurement of the number and deformity rate of spermatozoa,the activity of superoxide dismutase(SOD),the content of lipid peroxide(MDA),the expression of 3-nitrotyrosine(3-NT) in testicular tissue and the expression of 8-hydroxydeoxyguanosine(8-OHdG) in serum. Results Compared with the control group,the sperm count of the high dose group was lower,while the sperm deformity rate of the moderate and high dose groups and the high dose +NAC group was higher,the difference was statistically significant(P <0.05),and with the increase of the dose of organic extract,the sperm count decreased,while the sperm deformity rate increased;Compared with the high dose group,the sperm count was higher,but the sperm deformity rate was lower in the high dose +NAC group with significant difference(P <0.05).The number of spermatocytes in convoluted seminiferous tubule in each exposure group decreased significantly compared with that in control group(P<0.05),and decreased with the increase of exposure doses;The number of spermatogonia in convoluted seminiferous tubule in each exposure group had no significant difference compared with that in control group(P>0.05);Compared with the high dose group,the number of spermatocytes in high dose +NAC group increased significantly(P >0.05). Compared with the control group,higher levels of serum 8-OhdG were observed in high dose group and high dose+NAC group,higher levels of 3-NT in testicular tissue of mice were found in low,moderate and high dose groups and high dose + NAC group(P<0.05);While the levels of SOD and MDA in testicular tissue did not change significantly in each dose of organic extract group;The levels of SOD,MDA,3-NT in testicular tissue and serum 8-OhdG in mice showed an upward trend with the increase of exposure dose of organic extract.Compared with the high dose group,the levels of SOD,MDA,3-NT in testicular tissue and serum 8-OhdG in high dose +NAC group were significantly lower(P <0.05). Conclusion The organic extract from the Baotou reach of the Yellow River can affect the reproductive function of mice,and oxidative damage and DNA damage may be involved in it.