Zhou Qun, Hu Hai, Zhao Gang, Liu Ping, Wang Yixing, Zhang Hua
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Clinical Chinese Medicine, Key Laboratory of Liver and Kidney Diseases of Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, P.R. China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Exp Ther Med. 2021 Apr;21(4):316. doi: 10.3892/etm.2021.9747. Epub 2021 Feb 3.
The aim of the present study was to investigate the effects and the underlying mechanisms of Yinchenhao Decoction (YCHD), a traditional Chinese medicine formulation, on C57BL/6 mice with lithogenic diet (LD)-induced cholelithiasis. The condition of cholelithiasis was evaluated using a six-level criteria. Levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) in the serum and liver tissue were measured using enzyme colorimetry. Concentrations of TC, phospholipids (PL) and total bile acids (TBA) in the bile were measured to calculate the cholesterol saturation index. Liver histopathology was microscopically observed and mRNA expression levels of ABCG5, ABCG8, SRBI, ABCB4, ABCB11 and NPC1L1 involved in cholesterol metabolism were measured using reverse transcription-quantitative PCR. The results showed that feeding mice the LD induced cholelithiasis, along with abnormal serum biochemical indices and imbalances in biliary cholesterol homeostasis. Increased ALT and ALP levels in the serum and ALT, ALP, TC and LDL-C levels in the serum and liver indicated the existence of hepatocyte injury, which were consistent with the pathological changes. YCHD treatment ameliorated the serum and hepatic biochemical abnormalities and adjusted the biliary imbalance. In addition, elevated expression of ATP-binding cassette subfamily G member 5/8, scavenger receptor class B type I and Niemann-Pick C1 Like 1 in the liver and small intestine were observed at the onset of cholelithiasis but were reversed by YCHD. Taken together, results from the present study suggest that YCHD ameliorated LD-induced cholelithiasis mice, which may be caused by improvements in biliary cholesterol supersaturation and regulation of cholesterol metabolism.
本研究旨在探讨中药制剂茵陈蒿汤(YCHD)对喂食致石性饮食(LD)诱导的C57BL/6小鼠胆结石的影响及其潜在机制。采用六级标准评估胆结石状况。使用酶比色法测定血清和肝组织中丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平。测定胆汁中TC、磷脂(PL)和总胆汁酸(TBA)浓度以计算胆固醇饱和指数。显微镜下观察肝脏组织病理学变化,并使用逆转录定量PCR测定参与胆固醇代谢的ABCG5、ABCG8、SRBI、ABCB4、ABCB11和NPC1L1的mRNA表达水平。结果表明,给小鼠喂食LD可诱导胆结石形成,同时伴有血清生化指标异常和胆汁胆固醇稳态失衡。血清中ALT和ALP水平升高以及血清和肝脏中ALT、ALP、TC和LDL-C水平升高表明存在肝细胞损伤,这与病理变化一致。YCHD治疗改善了血清和肝脏生化异常,并调节了胆汁失衡。此外,在胆结石形成初期观察到肝脏和小肠中ATP结合盒转运体G家族成员5/8、B类I型清道夫受体和尼曼-皮克C1样蛋白1的表达升高,但YCHD可使其逆转。综上所述,本研究结果表明,YCHD改善了LD诱导的胆结石小鼠模型,这可能是由于胆汁胆固醇过饱和状态的改善和胆固醇代谢的调节所致。