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考察地高辛(digoxin,DIG)在大鼠卵巢摘除(ovariectomy,OVX)后体内药动学变化情况,并探讨其机制。将12只SD雌性大鼠随机分为两组,即OVX组和假手术组(n=6),OVX组打开腹腔摘除双侧卵巢缝合,假手术组打开腹腔后缝合,手术后正常饲养1个月,灌胃给予地高辛(2 mg·kg~(-1))。运用液质联用(LC-MS/MS)法测定地高辛的血药浓度,并采用Western blot法测定肠道P糖蛋白(P-glycoprotein,P-gp)的表达。口服给予地高辛后,与假手术组相比,OVX组AUC0-t无显著变化,但其C_(max)较假手术组显著降低(P<0.01),OVX组的肠道P-糖蛋白的表达较假手术组具有升高趋势但无显著性差异(P>0.05)。结果表明,卵巢摘除之后大鼠地高辛的C_(max)明显降低,可能与雌激素水平降低增加P-gp表达量有关。
To investigate the pharmacokinetics of digoxin (DIG) after ovariectomy (OVX) in rats and its mechanism. Twelve SD female rats were randomly divided into two groups: OVX group and sham operation group (n = 6). Ovarian suture was performed in OVX group and abdominal cavity was sutured in sham operation group and normal one Month, intragastric administration of digoxin (2 mg · kg -1)). The plasma concentration of digoxin was determined by LC-MS / MS, and the expression of P-glycoprotein (P-glycoprotein, P-gp) was detected by Western blot. After oral administration of digoxin, compared with sham operation group, AUC0-t in OVX group showed no significant change, but its C max was significantly lower than that in sham operation group (P <0.01). The intestinal P-glycoprotein (P> 0.05). However, there was no significant difference between the two groups (P> 0.05). The results showed that the C max of digoxin in ovariectomized rats decreased significantly, which may be related to the decrease of estrogen level and the increase of P-gp expression.