低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响

Effects of Low Molecular Weight Heparin on Inflammatory Response, Liver Function and Expression of Bcl-2 and Bax Proteins in Preeclampsia Rats

目的:研究低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响。方法:将90只孕期大鼠以随机数表法分成正常孕组、子痫前期组、治疗组,每组30只。其中子痫前期组和治疗组大鼠于妊娠第13 d开始皮下注射左旋硝基精氨酸甲酯,建立子痫前期大鼠模型,注射剂量为200 mg/(kg·d),正常孕组予以等量生理盐水注射干预。治疗组予以低分子肝素皮下注射干预,注射剂量为40μL/(kg·d),子痫前期组以及正常孕组大鼠予以同等剂量的生理盐水注射处理。比较三组大鼠的血压、24 h蛋白尿,肝功能指标水平,血清炎症因子水平,胎盘组织中Bcl-2及Bax蛋白表达水平。结果:子痫前期组及治疗组大鼠妊娠第15 d、21 d时的血压水平均显著高于正常孕组,且妊娠第21 d时的24 h蛋白尿高于正常孕组,治疗组大鼠妊娠第21 d的血压及24 h蛋白尿均低于子痫前期组(均P<0.05)。妊娠第21 d时子痫前期组、治疗组大鼠的谷丙转氨酶(ALT)、谷草转氨酶(AST)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、γ-干扰素(IFN-γ)水平均显著高于正常孕组,且治疗组低于子痫前期组(均P<0.05)。子痫前期组、治疗组大鼠胎盘组织中Bcl-2蛋白表达水平显著低于正常孕组,Bax蛋白表达水平显著高于正常孕组,且治疗组大鼠Bcl-2蛋白表达水平显著高于子痫前期组,Bax蛋白表达水平显著低于子痫前期组(均P<0.05)。结论:低分子肝素对子痫前期大鼠中具有明显的降血压效果,有利于改善大鼠肝功能,其主要作用机制可能与诱导Th1/Th2的平衡朝Th2方向发展,调节Bcl-2/Bax平衡有关。

Objective: To study the effects of low molecular weight heparin on inflammatory response, liver function and expression of Bcl-2 and Bax proteins in preeclampsia rats. Methods: A total of 90 pregnant rats were randomly divided into normal pregnant group, preeclampsia group and treatment group, with 30 rats in each group. The rats in the preeclampsia group and the treatment group were subcutaneously injected with l-nitroarginine methyl ester [200 mg/(kg·d)] on the 13 th day of gestation, and the rat model of preeclampsia was established. The normal pregnancy group was injected with the same dose of normal saline. The treatment group was treated with subcutaneous injection of low molecular weight heparin[ 40 μL/(kg·d)], and the rats in the preeclampsia group and normal pregnancy group were given the same dose of normal saline injections. Blood pressure, 24 h proteinuria, liver function index levels,serum inflammatory factor levels, and Bcl-2 and Bax protein expression levels in the placental tissues of the three groups were compared.Results: The blood pressure level of the preeclampsia group and the treatment group on the 15 th day of pregnancy and the 21 st day of pregnancy was significantly higher than that of the normal pregnancy group, and the 24 h proteinuria on the 21 st day of pregnancy was higher than that of the normal pregnancy group. The blood pressure and 24 h proteinuria of the treatment group on the 21 st day of pregnancy were lower than those of the preeclampsia group(all P <0.05). On the 21 st day of gestation, alanine aminotransferase(ALT),aminotransferase(AST), interleukin-2(IL-2), interleukin-6(IL-6) and γ-interferon(IFN-γ) in the preeclampsia group and the treatment group were significantly higher than those in the normal pregnancy group, and those in the treatment group were lower than those in the preeclampsia group(all P<0.05). The expression level of Bcl-2 protein in the placental tissues of the preeclampsia group and the treatment group were significantly lower than that of the normal pregnancy group, and the expression level of Bax protein was significantly higher than that of the normal pregnancy group. The expression level of Bcl-2 protein in the treatment group was significantly higher than that of the preeclampsia group, and the expression level of Bax protein was significantly lower than that of the preeclampsia group(all P<0.05). Conclusion: Low molecular weight heparin has a significant effect on blood pressure control in preeclampsia rats, and it is beneficial to improve liver function. The main mechanism may be related to inducing Th1/Th2 balance to develop towards Th2, and regulating Bcl-2/Bax balance.