Department of Medical Technology, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
Department of Medical Technology, Faculty of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan.
Exp Mol Pathol. 2020 Jun;114:104437. doi: 10.1016/j.yexmp.2020.104437. Epub 2020 Apr 1.
Nonalcoholic steatohepatitis (NASH) is linked to an increased risk of cardiovascular disease, regardless of the risk factors in metabolic syndrome. However, the intermediary factors between NASH and cardiovascular disease are still unknown. A previous study revealed that serum and hepatic bile acid (BA) levels are increased in some NASH patients. We aimed to examine whether NASH and cardiovascular disease were aggravated by BA using an animal model.
From 10 to 18 weeks of age, SHRSP5/Dmcr rats divided into 3 groups were fed 3 types of high-fat and high-cholesterol (HFC) diets which were changed in the cholic acid (CA) concentration (0%, 2%, or 4%). The nitro oxide synthase inhibition (L-NAME) was administered intraperitoneally from 16 to 18 weeks of age. The 4% CA groups showed the worst LV dysfunction and myocardial fibrosis, and demonstrated severe hepatic fibrosis and lipid depositions. In addition, a large amount of lipid accumulation was observed in the aortas of the 4% CA group, and NFκB and VCAM-1 gene expression levels were increased. These findings were not seen in the 0% CA group.
In the SHRSP5/Dmcr rat model, NASH and cardiovascular disease were aggravated with increasing BAs concentrations in an HFC diet.
非酒精性脂肪性肝炎（NASH）与心血管疾病风险增加相关，而不论代谢综合征中的危险因素如何。然而，NASH 与心血管疾病之间的中介因素仍不清楚。先前的一项研究表明，一些 NASH 患者的血清和肝胆汁酸（BA）水平升高。我们旨在使用动物模型检查 NASH 和心血管疾病是否因 BA 而加重。
从 10 至 18 周龄起，将 SHRSP5/Dmcr 大鼠分为 3 组，分别给予 3 种不同高胆固醇高脂肪（HFC）饮食，其中胆酸（CA）浓度分别为 0%、2%或 4%。从 16 至 18 周龄起，通过腹腔内注射给予一氧化氮合酶抑制剂（L-NAME）。4%CA 组表现出最差的 LV 功能障碍和心肌纤维化，并表现出严重的肝纤维化和脂质沉积。此外，在 4%CA 组的主动脉中观察到大量脂质堆积，NFκB 和 VCAM-1 基因表达水平增加。在 0%CA 组中未观察到这些发现。
在 SHRSP5/Dmcr 大鼠模型中，HFC 饮食中 BA 浓度的增加加重了 NASH 和心血管疾病。
