Teaching and Research Office of Clinical Foundation of Chinese Medicine, School of Basic Medicine, Innovation Team of ""Basic Research on the Application of Classical Formulas"", Beijing University of Chinese Medicine, Beijing 100029, China.
J Tradit Chin Med. 2020 Apr;40(2):253-266.
To evaluate the effectiveness of Sini powder for the treatment of non-alcoholic fatty liver disease (NAFLD) in rats and the molecular mechanisms involved.
A rat model of stress-induced NAFLD was established by a combination of long-term tethering and feeding of a high-fat, high-calorie diet. These rats were then intragastrically administered with either simvastatin, Sini powder, or vehicle for 1 week. The body mass and field test scores for each group were recorded weekly. Serum aspartate aminotransferase and alanine aminotransferase activities, and triglyceride, total cholesterol, and free fatty acid concentrations were measured. Liver tissue histopathology was examined on hematoxylin and eosin-stained paraffin sections and oil red O-stained frozen sections. The hepatic mRNA expression of nuclear factor kappa-B (NF-κB), NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 were measured by reverse transcription-polymerase chain reaction (RT-PCR). The hepatic protein concentrations of NF-κB and NLRP3, ASC, caspase-1, interleukin-1β (IL-1β), interleukin-6 (IL-6), and the serum concentrations of IL-1β and IL-6 were measured by enzyme-linked immunosorbent assay.
Compared with the Blank group, rats in the Compound model group showed significant pathologic manifestations of NAFLD, and the expression of NF-κB, NLRP3, ASC, caspase-1, IL-1β and IL-6 were significantly higher (all P < 0.01). Both simvastatin and Sini powder significantly ameliorated the NAFLD pathology and the abnormal expression of NF-κB, NLRP3, ASC, caspase-1, IL-1β, and IL-6 (all P < 0.01).
Sini powder inhibits the inflammatory response in rats with NAFLD, which is mediated by NF-κB/NLRP3, IL-1β, and IL-6, reduces the effects of psychological stress, and improves lipid metabolism. Therefore, Sini powder may be effective for the treatment of stress-related NAFLD through multiple mechanisms.
评价四逆散治疗大鼠非酒精性脂肪性肝病(NAFLD)的有效性及其相关分子机制。
采用长期束缚和高脂高糖饮食相结合的方法建立应激诱导的 NAFLD 大鼠模型。然后将这些大鼠分别给予辛伐他汀、四逆散或载体进行 1 周的灌胃治疗。每周记录各组大鼠的体重和现场测试评分。测定血清天门冬氨酸氨基转移酶和丙氨酸氨基转移酶活性以及三酰甘油、总胆固醇和游离脂肪酸浓度。苏木精-伊红染色石蜡切片和油红 O 染色冷冻切片检查肝组织病理学变化。采用逆转录-聚合酶链反应(RT-PCR)测定核因子 kappa-B(NF-κB)、NOD、LRR 和含pyrin 结构域蛋白 3(NLRP3)、凋亡相关斑点样蛋白(ASC)和半胱天冬酶-1 的肝组织 mRNA 表达。采用酶联免疫吸附试验(ELISA)测定 NF-κB 和 NLRP3、ASC、半胱天冬酶-1、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)的肝组织蛋白浓度和血清中 IL-1β和 IL-6 的浓度。
与空白组相比,复方模型组大鼠表现出明显的 NAFLD 病理表现,NF-κB、NLRP3、ASC、半胱天冬酶-1、IL-1β和 IL-6 的表达显著升高(均 P<0.01)。辛伐他汀和四逆散均能显著改善 NAFLD 病理和 NF-κB、NLRP3、ASC、半胱天冬酶-1、IL-1β和 IL-6 的异常表达(均 P<0.01)。
四逆散通过 NF-κB/NLRP3、IL-1β 和 IL-6 抑制 NAFLD 大鼠的炎症反应,减轻心理应激的影响,改善脂代谢,可能通过多种机制有效治疗应激相关的 NAFLD。