摘要
目的 :探讨青蒿琥酯 (Art)对胚胎发育的影响及其机理。方法 :选用 SD大鼠进行胚胎毒性研究 ,用DTNB直接法和 TBA法 ,测定胚胎和胎盘组织中谷胱甘肽过氧化物酶 (GSH- Px)的活性及脂质过氧化产物丙二醛(MDA)含量 ,细胞培养方法观察 Art对体外培养人蜕膜细胞存活率的影响。结果 :大鼠于妊娠 6～ 10 d皮下注射Art可产生胚胎毒性 ,引起胚胎吸收 ,并有剂量 -反应关系 (r=0 .996,P<0 .0 1)。末次给药后 2 4 h,胚胎中 GSH- Px活性显著降低 ,MDA含量显著升高 (P<0 .0 5 ) ,胎盘中 GSH- Px活性升高非常显著 (P<0 .0 1)。对体外培养的人蜕膜细胞有直接杀伤作用 ,其 LC50 为 (2 5 .2± 3.5 ) mg/ L。结论 :Art能破坏胚胎和胎盘的抗氧化系统的平衡状态 ,造成胚胎和胎盘组织的氧化损伤 ,并直接损伤蜕膜 ,最终导致胚胎吸收。
Objective: To examine the effect and mechanism of artesunate (Art) on embryo development. Methods: Rat embryo and placental glutathione peroxidase (GSH-Px)and malondialdehyde (MDA) were identified by using DTNB (dithionitrobenzene) direct method and TBA (thiobarbituric acid). We investigated the damage of decidual cells caused by Art using cell culture techniques. Results: Subcutaneous administration of Art in rats on d 6~ d 10 of gestation induced developmental toxicity. Absorption increased when progressively increased doses were given (r=0.996,P<0.01). Twenty-four hours post-injection, GSH-Px in embryo decreased significantly while MDA content was significantly higher than that in the control group (P<0.05). GSH-Px:study group was( 43.7± 10.7)μmol/min·mg -1Hb, control group was(54.5±10.1)μmol/min·mg -1Hb; MDA:study group was(230.2±19.8)nmol/g tissue, control group was(150.4±44.1)nmol/g tissue. Placental GSH-Px activity was significantly higher than that in the control group(P<0.01). After cultured human decidual cells were exposed to Art for 24 h, the LC 50 was (25.2±3.5)mg/L. Conclusion: Art may induce developmental toxicity in rat embryo and placenta by neutralizing the antioxidant defense mechanism.
出处
《浙江大学学报（医学版）》
CAS
CSCD
2003年第1期41-45,共5页
Journal of Zhejiang University(Medical Sciences)
基金
中科院新药研究国家重点实验室和浙江省计划生育委员会资助项目
