Banerjee Aryamitra, Padh Harish, Nivsarkar Manish
Department of Pharmacology and Toxicology, B. V. Patel Pharmaceutical Education and Research Development Centre, SG Highway, Thaltej, Ahmedabad, Gujarat, India.
J Basic Clin Physiol Pharmacol. 2009;20(1):43-53. doi: 10.1515/jbcpp.2009.20.1.43.
The proinflammatory blastocyst implantation cascade involves important mediators like prostaglandins (PG). The influx of calcium via the calcium channel acts as a trigger for the activation of the PG synthesis pathway. Hence, it was hypothesized that calcium channel blockers that are known to possess anti-inflammatory activity may interfere with normal implantation. Pregnant Swiss albino mice (Mus musculus) were treated with diltiazem (1) 4 mg/kg, po on days 1-6 of pregnancy, n=6/day) or (2) at the implantation site (25 microg/animal) via intrauterine injection in the right horn at 5:00 pm on day 4. The intact uterus was used to assay lipid peroxidation and superoxide dismutase activity as markers of membrane fluidity or to observe the day 15 fetus. Oral diltiazem treatment in therapeutic dosage before and during the implantation period did not cause any change in normal uterine milieu during the window of implantation. When injected into the uterine lumen 12-14 h before the average implantation time, however, a complete failure in implantation was observed. Thus, the site specific action of diltiazem may be blocking prostaglandin synthesis, hence causing implantation failure. Oral diltiazem treatment did not mimic this action, indicating that although orally safe in pregnancy in therapeutic dosage, calcium channel blockers may provide a new and yet unknown target in female contraceptive research.
促炎性胚泡着床级联反应涉及前列腺素（PG）等重要介质。通过钙通道的钙内流作为激活PG合成途径的触发因素。因此，有人推测已知具有抗炎活性的钙通道阻滞剂可能会干扰正常着床。将怀孕的瑞士白化小鼠（小家鼠）用以下方式给予地尔硫䓬：（1）在妊娠第1 - 6天口服，剂量为4 mg/kg，每天6只；或（2）在第4天下午5点通过子宫内注射到右角的着床部位（每只动物25μg）。完整的子宫用于检测脂质过氧化和超氧化物歧化酶活性，作为膜流动性的标志物，或观察第15天的胎儿。在着床期之前和期间给予治疗剂量的口服地尔硫䓬，在着床窗口期未引起正常子宫环境的任何变化。然而，在平均着床时间前12 - 14小时注入子宫腔时，观察到着床完全失败。因此，地尔硫䓬的位点特异性作用可能是阻断前列腺素合成，从而导致着床失败。口服地尔硫䓬治疗未模拟此作用，表明尽管治疗剂量在孕期口服安全，但钙通道阻滞剂可能在女性避孕研究中提供一个新的、尚不清楚的靶点。
