苯巴比妥、西咪替丁对醋氨酚致整体大鼠着床前胚泡毒性的影响

EFFECTS OF PHENOBARBITAL AND CIMETIDINE ONACETAMINOPHEN-INDUCED PREIMPLANTATION RATBLASTOCYST TOXICITIES IN VIVO

为探索醋氨酚（Ａｃｅ）致大鼠着床前胚泡毒性的机制，大鼠孕后以苯巴比妥（ｐｈｅ）或西咪替丁（Ｃｉｍ）预处理，并于孕ｄ３ｉｇＡｃｅ０．２５，０．５和ｌｇ／ｋｇ（阳性阴道涂片为孕ｄｏ）。ｄ４收集胚泡，观察其细胞数、微核率、有丝分裂指数和胚泡化作用。结果Ｐｈｅ预处理组胚泡微核率和具微核胚泡率显著升高，并与Ａｃｅ呈剂量依赖关系；而用Ｃｉｍ预处理组则呈微核率降低趋势，但胚泡平均细胞数显著减少。以上各组胚泡化作用与溶剂对照组无显著差异。揭示Ａｃｅ对整体大鼠着床前胚泡的细胞毒性主要由其本身引起，而遗传毒性则主要是由其经细胞色素Ｐ４５０氧化产生的代谢物所引起。Ａｃｅ及其代谢物对大鼠着床前胚胎的胚泡化作用均无显著影响。

Potential mechanisms of acetaminophen-induced rat blastocyst toxicities were e-valuated by pretreatment of phenobarbital (Phe)and cimetidine (Cim) to pregnant rats. Fe-rnale rats were treated with ig acetaminophen(Ace)0.25,0.5,and lg/kg on d3 of pregnancy(positive vaginal snllear=d0) after treating with ip Phe or Cim 24h and l.5h of the lastdose, respectively. Blastocysts were collected on d4 and evaluated for cell number, micronu-cleus, mitotic index, and blastulation.Areduction of cell number per blastocyst was discov-ered in the groups of maternal exposed to Ace 0.5 and lg/kg pretreated with Cim,meanwhileboth the frequency of micronuclei and frequency of blastocysts with micronuclei were in-creased in a dose-dependent manner when pretreated with Phe. Cim, however, had beenshowed to protect rat blastocysts from acetaminophen-induced micronnuclei but increasedthe cell toxicity. No markedly difference in blastulation between each tested group and con-trol group. The results demonstrated that the metabolites of Ace produced via cytochromeP450 were probably responsible to blastocysts for genetic toxicities,while Ace itself seem tomore toxic to cell in the rat blastocysts in vivo. Both Ace and its metabolites do not signifi-cantly influence the blastulation of preimplantation rat embryos.