穿心莲生殖毒性的量效关系研究

Research on relationship between dosing and effect of andrographis reproductive toxicity

研究穿心莲对雄性小鼠精子、酶活力及睾丸组织结构的影响,并探讨穿心莲对受试小鼠影响的量效关系.实验分为分为7组,每组25只,空白对照组(给予相应体积的蒸馏水),穿心莲内酯组(315 mg/kg),其他5组灌服穿心莲提取物,分别为穿心莲提取物A组(75.35 g/kg)、B组(34.88 g/kg)、C组(16.15 g/kg)、D组(7.48 g/kg)和E组(3.46 g/kg)经口灌胃,每天1次,给药持续11周.分别在给药的第3、5、7、9、11周剖杀受试小鼠,称量体重及睾丸和附睾重量,测定精子数量和精子畸形率,测定睾丸中乳酸脱氢酶(LDH)及碱性磷酸酶(AKP)的活性并制备睾丸病理切片.与对照组相比,受试小鼠的睾丸和附睾的相对质量均显著降低(P<0.01);小鼠精子数明显低于对照组,且在同一给药周期内,给药量越高降低程度越显著;精子畸形率高于对照组(P<0.05,P<0.01),且在同一给药周期内,给药量越高升高程度越显著;小鼠睾丸匀浆中LDH、AKP活性与对照组比较明显下降(P<0.05,P<0.01),且在同一给药周期内,降低程度与给药量成正比;受试小鼠的睾丸中曲细精管管壁变薄,管腔内成熟精子缺失;给药量越大出现损伤的程度越重.穿心莲提取物和穿心莲内酯对雄性小鼠具有生殖毒性作用,且存在一定的量-效关系.

This paper studied the effects of andrographis on male mice sperm, enzyme activity and organizational structure of testis, and discussed its dosing- effect relationship. The ex- periment were divided into seven groups （ n = 25, every group） ： control group, androgra- pholide （315 mg/kg）, andrographis extraction（A 75.35 g,/kg, B 34.88g/kg, C 16.15g/ kg, D 7.48g/kg, E 3.46g/kg） , by oral gavage and administrate 1 time each day, contin- ued for 77days（ll weeks）. Tested mice were killed on the 3, 5, 7, 9, 11 weeks of admin- istration. The weights of tested mice, hoden and nebenhoden were measured, sperm count and sperm deformity rate were detected. The testis pathological were prepared, at the same time, the activities of lactate dehydrogenase （LDH） and alkaline phosphatase （AKP） of tes- tis were also measured. Compared with the control group, relative weight of testis and epi- didymis decreased significantly （P 〈 0.05 ） ; sperm count was significantly lower than thecontrol group, and in the same period of administration, the dose was higher, the degree of reduction was more significant. Compared with the control group, sperm deformity rate was higher （P 〈 0. 05, P 〈 0.01 ）, and in the same period of administration, the dose was high- er, the degree of increase was more significant. Testis homogenate LDH, AKP activity was significantly decreased compared with the control group （ P 〈 0. 05, P 〈 0.01 ）, and in the same period of administration, dosage was proportional to the degree of reduction. Seminifer- ous tubules wall of mice testes was thin and mature sperms within the lumen was lost. An- drographis extraction and andrographolide have reproductive toxicity effects on male mice, and its toxicity exist has certain dosing- effect relationship.