低分子肝素抑制子痫前期样大鼠胎盘细胞凋亡

目的研究低分子肝素(LMWH)对子痫前期样大鼠胎盘组织的抗细胞凋亡作用。方法将孕鼠随机分为正常孕组、子痫前期组(PE组)及LMWH治疗组,每组10只。PE组及LMWH治疗组孕鼠均于妊娠第13天开始给予左旋硝基精氨酸甲酯(L-NAME)200 mg(/kg.d)皮下注射,共4 d,建立子痫前期样孕鼠模型。PE组于妊娠第15~20天给予生理盐水0.5 ml皮下注射,LMWH治疗组于妊娠第15~20天给予LMWH 40μl(/kg.d)皮下注射。检测各组血压、尿蛋白、鼠胎数、鼠胎质量及胎盘质量,对LMWH疗效进行评价;采用TUNEL法检测胎盘细胞凋亡率,Western blotting法检测胎盘组织中活化caspase-3、Bcl-2及Bax蛋白表达。结果 PE组大鼠血压及尿蛋白均显著高于正常孕组(P<0.05),鼠胎数及鼠胎质量显著降低(P<0.05)。LMWH治疗组血压及尿蛋白较PE组明显降低(P<0.05),但仍显著高于正常孕组(P<0.05),鼠胎数及鼠胎质量较PE组显著增高(P<0.05),鼠胎质量显著低于正常孕组(P<0.05),而鼠胎数与正常孕组无显著差异(P>0.05)。与正常孕组相比,PE组胎盘组织细胞凋亡率显著升高(P<0.05),活化caspase-3及Bax蛋白表达显著升高(P<0.05),而Bcl-2蛋白表达则显著降低(P<0.05);LMWH治疗组胎盘凋亡率及活化caspase-3蛋白表达较PE组显著降低(P<0.05),Bcl-2显著升高,而Bax则显著降低(P<0.05),与正常孕组比均无显著差异(P>0.05)。结论 LMWH可以有效改善子痫前期样症状,减少子痫前期样大鼠胎盘细胞凋亡,这一作用可能通过调节Bcl-2/Bax平衡抑制细胞凋亡。

Low molecular weight heparin inhibits cell apoptosis in the placenta of rats with preeclampsia-like symptoms

Objective To investigate the anti-apoptotic effect of low molecular weight heparin(LMWH) in the placenta of rats with preeclampsia-like symptoms.Methods Thirty pregnant Wistar rats were randomized equally into 3 groups and received subcutaneous saline injection(control group),200 mg/kg L-NAME injection to induce preeclampsia symptoms(PE group),or L-NAME with 40 μl/kg LMWH injections(LMWH group).The blood pressure,urine protein,the number of pups and the weight of the fetuses and placenta were measured,and the placental apoptotic index was measured by TUNEL assay.The expression of cleaved caspase-3,Bcl-2 and Bax in the placenta were examined by Western blotting.Results Compared with the control group,L-NAME injections caused significantly increased blood pressure and urine protein(P<0.05),which were significantly lowered by LWMH(P<0.05).The number and weight of normal pups were significantly lower in PE group than in the control group(P<0.05) and LMWH group(P<0.05);in LMWH group,the weight of pups was still lower than that of the control group(P<0.05) but the number of normal pups was comparable(P>0.05).The LMWH group showed a significantly lower placental apoptosis index than the PE group(P<0.05) with also significantly lower cleaved caspase-3 and Bax and higher Bcl-2 expressions(P<0.05).The apoptosis index and expressions of cleaved caspase-3,Bcl-2 and Bax protein were similar between LMWH group and normal pregnant group(P>0.05).Conclusion LMWH can alleviate preeclampsia-like symptoms and decrease the apoptosis in the placenta of rats possibly by enhancing Bcl-2 and suppressing Bax expressions.