孕期炎症刺激对子代大鼠血脂水平的影响

Effect of Maternal LPS Exposure During Pregnancy on Blood Lipids in Offspring Rats

目的研究孕期炎症刺激对子代大鼠血脂水平的影响。方法 8只SD孕鼠随机分为对照组和脂多糖刺激组,分别在孕第8、10、12天腹腔注射生理盐水或脂多糖(0.79 mg/kg)。子代出生1天及每周测体重;检测8周龄雄性仔鼠血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、谷草转氨酶(AST)、谷丙转氨酶(ALT)水平;组织切片观察子代肝脏病理形态学变化;透射电镜观察肝、胸主动脉超微结构;免疫荧光检测仔鼠肝脏8-OHd G表达情况;TMRE染色检测线粒体膜电位。结果与对照组子代相比,脂多糖刺激组子代1天、1周龄体重下降(P<0.01),而后体重显著增加(P<0.01)。脂多糖刺激组子代8周龄外周血TG、TC、LDL及AST水平与对照组子代相比显著升高(P<0.05或P<0.01);肝脏病理改变明显,线粒体结构显著损伤,8-OHd G表达增多,肝脏线粒体膜电位较对照组子代明显降低(P<0.01);胸主动脉表现出内皮脱落、平滑肌细胞迁移为特征的损伤。结论孕期炎症刺激导致子代线粒体损伤,可能与脂质代谢障碍并最终导致动脉粥样硬化发生相关。

Aim To explore the role of prenatal exposure to lipopolysaccharides（ LPS） on blood lipids in offspring rats. Methods Eight pregnant rats were randomly divided into control group and LPS group. The rats in these groups were intraperitoneally administered with vehicle or LPS 0. 79 mg / kg on the 8 th,10 th and 12 th days,respectively. Liver histopathological alteration was observed by hematoxylin-eosin staining and transmission electron microscopy,8-OHd G expression was determined by confocal laser-scanning microscope and mitochondrial potential was detected by microplate reader in 8-week-old offsprings. Simultaneously,the body weight was measured in offsprings weekly and at day 1. Results By comparison of those offsprings in control group,body weight of offspring rats in 1 day and 1 week were both significantly decreased（ P〈0. 01）. Whereafter,the body weight of offsprings in LPS group were increased obviously from 2 nd week to 8th week（ P〈0. 01）. Compared with offsprings from control group,there were dramatic increases in the serum level of TG,TC,LDL and AST（ P〈0. 05 or P〈0. 01）. In 8-week-old LPS offsprings,the liver exhibited significant lesions,in particular mitochondrial pathological alterations. The functional analysis of mitochondria suggested the expression of 8-OHd G increased obviously,and the mitochondrial potential decreased significantly in offsprings of LPS group（ P〈0. 01）. Furthermore,the thoracic aortas exhibited lesions,including impaired endothelial cells,and migration and proliferation of vascular smooth muscle cells. Conclusion Our results indicate that maternal LPS exposure during pregnancy leads to mitochondrial dysfunction in offspring that predispose to disorder of blood lipids and even atherosclerosis in adult.