Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China; Guangzhou Medical College, Guangzhou, China; Departments of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou, China; Departments of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
Am J Obstet Gynecol. 2014 Nov;211(5):538.e1-7. doi: 10.1016/j.ajog.2014.04.026. Epub 2014 Apr 23.
The objective of the study was to examine the effects of nicotine, an α7 nicotinic acetylcholine receptor agonist, on lipopolysaccharide (LPS)-induced inflammatory responses in rats during pregnancy.
Pregnant Sprague Dawley rats were randomly divided into groups (n = 6 rats/group): group 1 rats each received a single intraperitoneal injection of LPS (25 μg/kg) on gestation day 16; group 2 rats were first pretreated with nicotine (1 mg/kg per day, subcutaneously) on gestation days 14 and 15 and then were treated with single injections of LPS on gestational day 16; group 3 rats were treated with the vehicle (saline) used for groups 2 and 3 (controls). Maternal blood was collected at 6 hours and 24 hours after LPS and vehicle treatments and assayed for tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and interleukin-10 (IL-10). In addition, the number of live pups and pup weights were obtained at the time of delivery.
LPS treatment significantly (P < .001) elevates maternal blood levels of TNF-α and IL-6 but not IL-10 (P > .05). Nicotine treatment significantly reduces LPS-induced TNF-α and IL-6 concentrations (P < .001) but does not change (P > .05) IL-10 levels. The number of live pups in the LPS group are significantly lower (P < .001) than the vehicle treated controls, and nicotine treatment significantly (P < .011) reverses this change. Similarly, fetal weights are lower following LPS (P < .016) and higher (P < .024) in the group treated with nicotine plus LPS.
Nicotine reduces the LPS-induced inflammatory responses and rescues the fetus in rats during pregnancy. Thus, nicotine exerts dramatic antiinflammatory effects. These observations have important implications for control of inflammatory responses during pregnancy.
本研究旨在探讨尼古丁（一种α7 烟碱型乙酰胆碱受体激动剂）对妊娠大鼠脂多糖（LPS）诱导的炎症反应的影响。
将妊娠 Sprague Dawley 大鼠随机分为以下几组（每组 6 只大鼠）：第 1 组大鼠于妊娠第 16 天单次腹腔注射 LPS（25μg/kg）；第 2 组大鼠于妊娠第 14 天和第 15 天每天皮下注射尼古丁（1mg/kg），然后于妊娠第 16 天单次注射 LPS；第 3 组大鼠给予第 2 组和第 3 组所用的载体（生理盐水）（对照组）。在 LPS 和载体处理后 6 小时和 24 小时采集母鼠血液，检测肿瘤坏死因子（TNF）-α、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）的水平。此外，在分娩时还获得了活产仔数和仔鼠体重。
LPS 处理显著（P <.001）升高了母鼠血液中 TNF-α和 IL-6的水平，但不改变 IL-10 的水平（P >.05）。尼古丁处理显著降低了 LPS 诱导的 TNF-α和 IL-6浓度（P <.001），但不改变（P >.05）IL-10 水平。LPS 组的活产仔数明显低于载体处理对照组（P <.001），而尼古丁处理显著（P <.011）逆转了这一变化。同样，LPS 处理组的胎鼠体重较低（P <.016），而尼古丁加 LPS 处理组的胎鼠体重较高（P <.024）。
尼古丁降低了 LPS 诱导的炎症反应，并挽救了妊娠大鼠的胎儿。因此，尼古丁发挥了显著的抗炎作用。这些观察结果对控制妊娠期间的炎症反应具有重要意义。
