Interaction among abnormal fatty acid oxidation,endothelial function disorder,and oxidative stress in the onset of severe preeclampsia

目的 探讨脂肪酸氧化代谢异常和内皮细胞功能障碍与氧化应激三者之间在重度子病前期发病机制中的相互作用.方法 采用免疫组织化学SP法,检测70例不同起病时间的重度子痫前期伴或不伴有肝损害患者的胎盘组织中长链L-3-羟酰基辅酶A脱氢酶(LCHAD)、肿瘤坏死因子(TNF)-α、血管细胞黏附分子-1(VCAM-1)和过氧化物酶体增殖物激活受体-γ(PPARγ)的蛋白表达,并与54例早、中、晚期正常妊娠绒毛和胎盘组织作比较.结果 正常妊娠和重度子痫前期胎盘组织均有LCHAD、TNF-α、VCAM-1和PPARγ的表达.LCHAD表达强度在发病孕周小于32周的重度子痫前期组与对照组比较明显降低,差异有统计学意义(P<0.05),其中有肝损害患者的LCHAD表达强度降低更为明显[(8.2±2.5)积分A值及(17.3±4.5)积分A值].而发病孕周大于32孕周的重度子痫前期各组与对照组比较则无明显变化.不同发病孕周重度子痫前期组TNF-α表达强度较对照组均明显增加,差异有统计学意义(P<0.05);VCAM-1表达强度在发病为32～34孕周的重度子痈前期不伴肝功损害组以及发病为34孕周后的重度子痫前期组,较对照组均明显增加,差异有统计学意义(P<0.05).不同发病孕周的重度子痫前期组与对照组比较,PPARγ表达强度变化差异无统计学意义.发病孕周<32周和>32周的重度子痫前期患者,LCHAD、TNF-α、和VCAM-1、PPARγ4者之间无线性相关性.结论 脂肪酸氧化代谢异常可能与某些较早发生的重度子痫前期(发病孕周<32周)有一定关系,尤其是早发型伴有肝损害者,脂肪酸氧化代谢异常可能参与某些患者疾病的发生发展;LCHAD与TNF-α、VCAM-1、PPARγ之间可能存在着复杂的调节机制.Objective To investigate the association of abnormal fatty acid oxidation(FAO), endothelial function activation, and oxidative stress in pathogenesis of severe preeclampsia (S-PE).Methods Placema tissues were obtained from 70 S-PE patients with onset in different gestational weeks with or without liver damage.The protein expression of long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD),tumor necrosis factor(TNF)-α,vascular cell adhesion molecule(VCAM)-1,and peroxisome proliferator activated receptor(PPAR)γ were analyzed using immunohistochemistry.54 samples from normal prenancy in first,second and third trimester were collected as controls. Results Protein expression of LCHAD.TNF-α,VCAM-1,and PPAR-γ could be seen in both placenta of normal pregnancy and S-PE.The protein expression level of LCHAD of the cases of S-PE that came down of the disease before 32 gestational weeks,especially of the cases complicated with liver damage,Was significantly lower than that of the controls(P<0.05).However,no differences in the LCHAD protein expression were found between the S-PE patients with the onset after and 32 gestational weeks and the controls.The TNF-α protein expression levels of the S-PE patients with different onset weeks were all significantly higher than those of the controls (all P<0.05).The VCAM-1 protein expression levels of the S-PE patients with the onset after 34-gestational weeks was significantly higher than that of the controls(P<0.05).There Was no significant diffference in the PPARγ protein expression between the S-PE patients and the controls.The placental LCHAD protein expression of the S-PE patients with the onset before 32 gestational weeks,especially of the cases with liver function damage,was dramatically decreased in comparison with the controls.and the placental TNF-α protein expression was dramatically increased,however,there was no linear cofrelation between LCHAD and TNF-α expression.There was no significant difference in expression of PPARγ and VCAM-1 between the S-PE patients and the controls.There was no linear correlation among the exDIlession levels of LCHAD,TNF-α,VCAM-1,and PPARγbetween the S-PE patients with the onset before and after 32 gestation weeks. Conclusion Abnormal FAO may be one of the factors related to some cases of PE with the onset before 32 gestational-weeks,especially those with liver damage.The Correlation among LCHAD,TNF-α,VCAM-1,and PPARγare complicated.国家自然科学基金; 首都医学发展科研项目PubMed中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)0211471-14758