Nyakudya T T, Mukwevho E, Nkomozepi P, Erlwanger K H
1School of Physiology, Faculty of Health Sciences,University of the Witwatersrand,Johannesburg,South Africa.
3Department of Biology, Faculty of Agriculture, Science and Technology,North West University,Mmabatho,Mafikeng,South Africa.
J Dev Orig Health Dis. 2018 Oct;9(5):500-510. doi: 10.1017/S2040174418000259. Epub 2018 May 24.
Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47-49% increase in hepatic lipid content of both male and female rats (P<0.05). However, fructose administered in adulthood only, caused a significant increase (P<0.05) in liver lipid content in females only. NAFLD activity scores for inflammation and steatosis were higher in the fructose-fed rats compared with other groups (P<0.05). Steatosis, low-grade inflammation and fibrosis were observed in rats that received HF+F. NAFLD area fraction for fibrosis was three times higher in rats that received fructose neonatally and in adulthood compared with the rats in the negative control group (P<0.05). Treatment with OA during a critical window of developmental plasticity in rats prevented the development of fructose-induced NAFLD.
出生后早期的饮食干预与包括非酒精性脂肪性肝病（NAFLD）在内的代谢紊乱的发生或对代谢功能障碍的长期保护有关。我们研究了植物化学物质齐墩果酸（OA）新生期给药对成年后饮食果糖诱导的NAFLD后续发展的潜在肝脏保护作用。将雄性和雌性乳鼠（n = 112）用蒸馏水（DW）、OA（60 mg/kg）、高果糖溶液（HF；20% w/v）和OA+HF（OAHF）灌胃7天。在第21天至第55天，将大鼠断奶并给予正常大鼠饲料。从第56天起，每个治疗组的一半大鼠继续饮用普通水或HF作为饮用水，持续8周。然后测定肝脏脂质蓄积和肝脏组织形态学。新生期摄入果糖（HF+F）后成年期摄入果糖导致雄性和雌性大鼠肝脏脂质含量增加47 - 49%（P<0.05）。然而，仅在成年期给予果糖仅导致雌性大鼠肝脏脂质含量显著增加（P<0.05）。与其他组相比，果糖喂养的大鼠的NAFLD炎症和脂肪变性活动评分更高（P<0.05）。在接受HF+F的大鼠中观察到脂肪变性、轻度炎症和纤维化。与阴性对照组相比，新生期和成年期均接受果糖的大鼠的NAFLD纤维化面积分数高出三倍（P<0.05）。在大鼠发育可塑性的关键窗口期用OA治疗可预防果糖诱导的NAFLD的发生。
