Kim Eung Ju, Kim Baek-hui, Seo Hong Seog, Lee Yong Jik, Kim Hyun Hee, Son Hyun-Hwa, Choi Man Ho
Cardiovascular Center, Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
PLoS One. 2014 Jun 5;9(6):e97841. doi: 10.1371/journal.pone.0097841. eCollection 2014.
Although triglyceride accumulation in the liver causes non-alcoholic fatty liver disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as atherosclerosis. However, NAFLD and atherosclerosis have not been investigated simultaneously in animal models fed a high-cholesterol diet. Moreover, it is unclear whether systemic inflammation can exacerbate both pathologies in the same model. Accordingly, this study investigated the effect of additional systemic inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild animals. New Zealand white rabbits were divided into 4 groups: groups I (control) and II received normal chow, and groups III and IV received a 1% cholesterol diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3 weeks. After 3 months, total cholesterol markedly increased in groups III and IV, and the serum expressions of systemic inflammatory markers were elevated in the groups II-IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of foam cells) were observed in both the liver and aorta specimens from group III, and advanced lesions were observed in group IV. The expressions of inflammatory cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group I to IV but were similar in the liver in groups II-IV. Cholesteryl ester (CE) levels were higher in group IV than in group III, although the difference was not significant. CE levels in the aorta were similar between groups III and IV. Systemic inflammation can simultaneously exacerbate existing early lesions due to cholesterol overload in both the liver and aorta of rabbits. However, the cellular response of inflammatory receptors and expression of cholesterol metabolites differ between these organs.
虽然肝脏中甘油三酯的积累会导致非酒精性脂肪性肝病（NAFLD），但高胆固醇血症也是NAFLD以及动脉粥样硬化的主要原因。然而，在喂食高胆固醇饮食的动物模型中，尚未同时对NAFLD和动脉粥样硬化进行研究。此外，尚不清楚全身炎症是否会在同一模型中加剧这两种病症。因此，本研究调查了额外的全身炎症对野生动物中胆固醇超载诱导的NAFLD和动脉粥样硬化的影响。将新西兰白兔分为4组：第I组（对照组）和第II组喂食正常饲料，第III组和第IV组喂食1%胆固醇饮食。为了通过Toll样受体（TLR）-4信号通路诱导炎症，第II组和第IV组每3周皮下注射0.5 mL 1%角叉菜胶。3个月后，第III组和第IV组的总胆固醇显著升高，第II-IV组全身炎症标志物的血清表达升高。在第III组的肝脏和主动脉标本中均观察到早期NAFLD病变（例如肝脏中伴有散在纤维化的轻度脂肪变化）和动脉粥样硬化（例如由泡沫细胞组成的内膜增生），在第IV组中观察到晚期病变。主动脉中炎症细胞受体TLR-2和TLR-4的表达从第I组到第IV组逐渐增加，但在第II-IV组的肝脏中相似。第IV组的胆固醇酯（CE）水平高于第III组，尽管差异不显著。第III组和第IV组主动脉中的CE水平相似。全身炎症可同时加剧兔子肝脏和主动脉中由于胆固醇超载而现有的早期病变。然而，这些器官中炎症受体的细胞反应和胆固醇代谢产物的表达有所不同。
