低分子肝素钙对子痫前期大鼠炎性细胞因子的影响

Effects of Low Molecular Weight Heparin Calcium on Inflammatory Cytokines in Rats with Pre-Eclampsia

探讨低分子肝素钙对子痫前期大鼠炎性细胞因子的影响。将Wistar大鼠随机分为A组、B组、C组和D组共4组（n=10）,A组和B组大鼠均在妊娠2周后连续5 d注射剂量为200 mg·kg^-1·d^-1的L-NAME,此后,A组连续5 d注射剂量为50μg·kg^-1·d^-1的低分子肝素钙注射液,B组连续5 d注射0.5 m L/d生理盐水。C组大鼠为正常妊娠组,妊娠2周后连续10 d注射0.5 m L/d生理盐水。D组大鼠为非妊娠对照组,用药过程中注射0.5 m L/d生理盐水。通过ELISA、免疫组化、荧光定量PCR、Western blotting检测各组大鼠外周血、胎盘、肾脏和脾脏中IFN-γ、IL-2、IL-4和IL-6炎性细胞因子水平的变化。结果显示,B组IFN-γ和IL-2在外周血、胎盘、肾脏和脾脏的表达水平明显高于C组,而IL-4和IL-6的表达水平均明显低于C组（p〈0.05）;A组IFN-γ和IL-2的表达水平均明显低于B组,且IL-4和IL-6表达水平与B组相比,其表达水平明显升高（p〈0.05）。本研究所建立的动物模型可使Th1/Th2发生Th1方向漂移,可以用来模拟子痫前期的免疫失衡;低分子肝素钙可明显抑制促炎性细胞因子的分泌,促进抗炎细胞因子的分泌,可使Th1/Th2的平衡向Th2方向漂移,从而表现出良好的抗炎作用。

To investigate the effect of low molecular weight heparin calcium on inflammatory cytokines in preeclampsia rats. Wistar rats were randomly divided into group A, group B, group C and group D（n=10）. Group A and group B rats were given L-NAME at a dose of 200 mg·kg^-1·d^-1 for 5 consecutive days after 2 weeks of gestation. After which group A was injected with low molecular weight heparin calcium at a dose of 50 μg·kg^-1·d^-1 for 5 days, and group B was injected with 0.5 m L/d saline for 5 days. Rats in group C were in normal pregnancy group, and 0.5 m L/d normal saline was injected for 10 consecutive days after 2 weeks of gestation. Rats in group D were non-pregnant control group, and 0.5 m L/d normal saline was injected during the administration. The levels of IFN-γ, IL-2, IL-4 and IL-6 inflammatory cytokines in peripheral blood, placenta, kidney and spleen of each group were detected by ELISA, immunohistochemistry, real-time PCR and Western blotting. The results showed that the expression levels of IFN-γ and IL-2 in peripheral blood, placenta, kidney and spleen of group B were significantly higher than those of group C, while the expression levels of IL-4 and IL-6 were significantly lower than those of group C（p〈0.05）; The expression levels of IFN-γ and IL-2 in group A were significantly lower than those in group B, and the expression levels of IL-4 and IL-6 were significantly higher than those in group B（p 0.05）. The animal model established in this study can cause Th1/Th2 to drift in Th1 direction, which can be used to simulate the immune imbalance of preeclampsia; low molecular weight heparin calcium can significantly inhibit the secretion of pro-inflammatory cytokines and promote the secretion of anti-inflammatory cytokines. The balance of Th1/Th2 can be shifted to the Th2 direction, thereby exhibiting a good anti-inflammatory effect.