西曲瑞克和曲普瑞林对小鼠免疫效应的对比实验研究

Comparative researches on immunization efficacy of Cetrorelix and Triptorelin in mice

目的探讨促性腺激素释放激素拮抗剂和激动剂抗原主动免疫对小鼠免疫效果、生长与器官发育和生殖内分泌的作用。方法 105只昆明雌鼠随机均分为西曲瑞克组(CET)、曲普瑞林组(TRI)和对照组(CG),在CET-1、CET-2及CET-3小组分别皮下注射曲普瑞林抗原0.1、0.2及0.4 ml,TRI-1、TRI-2及TRI-3小组分别皮下注射西曲瑞克抗原0.1、0.2及0.4 ml,CG组注射生理盐水0.2 ml,各组均连续注射7 d。精确测定体质量,于0、21及35 d从各小组分别抓取5只小鼠眼眶后静脉丛采血,分离血清;同时断颈处死,无菌采集心脏、肝脏、脾脏、肾脏、子宫及卵巢,分别称质量,计算日增质量和内脏指数。ELISA试剂盒测定血清Gn RH抗体、LH和Gn RH质量浓度。结果实验期间CET-3组体质量大于CG组(P<0.01),CET-1和CET-2组小鼠体质量在12 d和21 d时小于CG组(P<0.05);8 d后TRI-1小组体质量低于CG组(P<0.05);TRI-2和TRI-3组分别于16 d和21 d降至低谷。CET-3和TRI-1组肝脏与脾脏质量均明显大于CG(P<0.05),35 d时CET-3、TRI-1、TRI-2和TRI-3组子宫质量分别减小31.63%、21.55%、63.1%和61.71%;CET-1和CET-2组子宫质量比CG增加40.78%和11.94%。CET和TRI的血清Gn RH抗体浓度高于CG,且TRI组的高于CET组,尤其是TRI-3组更明显(P<0.01)。21 d各实验组Gn RH质量浓度均低于CG,TRI-3组显著低于CG(P<0.05)。至35 d,CET-1、CET-2、TRI-2和TRI-3组Gn RH质量浓度显著低于CG(P<0.05),CET-3组则高于CG。CET-3和TRI-3组血清LH质量浓度显著低于CG。结论西曲瑞克和曲普瑞林主动免疫能剂量依赖性地促进机体产生Gn RH抗体,免疫抑制Gn RH和LH合成与分泌,低剂量免疫注射初期抑制小鼠生长,高剂量后期明显促进肝脏和脾脏的生长发育、抑制子宫发育,且曲普瑞林的作用更加明显。

The study aims to investigate the immunization efficacy of gonadotropin-releasing hormone （GnRH） antagonist and agonist antigens active immunization on the growth, development and hormones secretion in mice. 105 mice were randomly assigned into Cetrorelix （CET）, Triptorelin （TRI） and control groups （CG）. Mice in CET-1, CET-2 and CET-3 subgroups were subcutaneously injected with cetrorelix antigen at 0.1, 0.2 and 0.4 ml, respectively once a day on seven consecutive days. Animals in TR1-1, TR1-2 and TR1-3 subgroups were subcutaneously injected with Triptorelin antigen at 0.1, 0.2 and 0.4 ml, respectively once a day on seven consecutive days. Mice in CG were injected with 0.2 ml saline for seven days, once a day. All mice were accurately weighed each day using an electronic balance. Blood samples were taken and serum was separated on days 0, 21 and 35, and serum contents of GnRH antibody, LH and GnRH were determined. Samples of heart, liver, spleen kidney, stomach, uterus and ovaries were collected aseptically at the same time. The results showed that body weight of CET-3 subgroup were greater than that of CG （P〈 0.01）. However. bodv weights of CET-I. CET-2 （on days 12 and 21） and TRI-1 （on day 8） were less than that of CG （P〈 0.05）. Body weights of CET-1, TRI-2 and TRI-3 arrived at the bottoms on days 12, 16 and 21, respectively （P〈 0.05）. The liver and spleen weights of CET-3 and TRI-1 were significantly larger than that of CG （P〈 0.05）. On day 35, uterine weights of CET-3, TRI-1, TRI-2 and TRI-3 were reduced by 31.63%, 21.55%, 63.1% and 61.71%, respectively. Serum concentrations of GnRH antibody in CET and TRI groups were higher than that of CG group, and increased dose- dependently with a maximum in TRI-3 （P〈 0.01）. Serum concentrations of GnRH and LH in both CET and TRI groups were less than that of CG during the experiment. In conclusion, injecting antigens of Cetrorelix and Triptorelin could produce GnRH antibody, which could inhibit the synthesis and secretion of GnRH and LH. Cetrorelix and Triptorelin antigen at low dose inhibit growth and liver, spleen as well as uterus development of mice at the initial stage. High doses of Cetrorelix and Triptorelin have promotion effects. Triptorelin was more effective than cetrorelix.