Chen Ping, Li Yusheng, Xiao Li
Department of Pharmacy, Affiliated Hospital of Shandong Medical College, Linyi, Shandong 276000, P.R. China.
Department of Pharmacy, Linyi Maternal and Child Health Care Hospital, Linyi, Shandong 276000, P.R. China.
Exp Ther Med. 2021 Oct;22(4):1109. doi: 10.3892/etm.2021.10543. Epub 2021 Aug 3.
The global incidence of nonalcoholic fatty liver disease (NAFLD) is increasing. The present study explored the effect and mechanism of berberine (BBR) on NAFLD in rats. Thirty-five Sprague-Dawley rats were randomly divided into the control and NAFLD groups, which were fed a normal diet or high-fat diet, respectively, for 8 weeks. Hematoxylin and eosin staining was performed on liver tissues and establishment of the NAFLD model was confirmed by microscopy. NAFLD rats were subsequently randomly subdivided and treated with saline or BBR for 8 weeks. The liver wet weight of rats in each group was measured, the liver tissue structure was observed by microscopy, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), fasting blood glucose (FBG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels were detected using a semi-automatic biochemical detector. Reverse transcription-quantitative PCR and western blotting were performed to determine the mRNA and protein expression levels of microsomal triglyceride transfer protein (MTTP), apolipoprotein B and low-density lipoprotein receptor (LDLR). Compared with the control group, the liver wet weight of the NAFLD rats was higher; the liver showed obvious fatty degeneration and liver TG levels increased significantly, as did serum levels of ALT, AST, TC, TG, FBG, HDL and LDL, while expression of MTTP and LDLR significantly decreased. Compared with the saline-treated NAFLD rats, the BBR-treated rats had reduced liver wet weight, improved liver steatosis and a significant decrease in liver TG levels, while ALT, AST, TC, TG, and LDL serum levels significantly decreased and MTTP levels were significantly upregulated. In conclusion, BBR treatment ameliorated the fatty liver induced by a high-fat diet in rats. Furthermore, BBR reversed the abnormal expression of MTTP and LDLR in rats with high-fat diet induced-NAFLD. The present findings suggest that fatty liver could be improved by BBR administration, via reversing the abnormal expression of MTTP and LDLR and inhibiting lipid synthesis.
非酒精性脂肪性肝病（NAFLD）的全球发病率正在上升。本研究探讨了小檗碱（BBR）对大鼠非酒精性脂肪性肝病的影响及其机制。将35只Sprague-Dawley大鼠随机分为对照组和非酒精性脂肪性肝病组，分别给予正常饮食或高脂饮食8周。对肝组织进行苏木精-伊红染色，并通过显微镜检查确认非酒精性脂肪性肝病模型的建立。随后，将非酒精性脂肪性肝病大鼠随机再分为两组，分别用生理盐水或小檗碱治疗8周。测量每组大鼠的肝脏湿重，通过显微镜观察肝组织结构，并使用半自动生化检测仪检测丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆固醇（TC）、甘油三酯（TG）、空腹血糖（FBG）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）水平。进行逆转录定量PCR和蛋白质印迹法以测定微粒体甘油三酯转移蛋白（MTTP）、载脂蛋白B和低密度脂蛋白受体（LDLR）的mRNA和蛋白表达水平。与对照组相比，非酒精性脂肪性肝病大鼠的肝脏湿重更高；肝脏出现明显的脂肪变性，肝脏甘油三酯水平显著升高，血清ALT、AST、TC、TG、FBG、HDL和LDL水平也升高，而MTTP和LDLR的表达显著降低。与生理盐水治疗的非酒精性脂肪性肝病大鼠相比，小檗碱治疗的大鼠肝脏湿重减轻，肝脂肪变性改善，肝脏甘油三酯水平显著降低，而血清ALT、AST、TC、TG和LDL水平显著降低，MTTP水平显著上调。总之，小檗碱治疗改善了高脂饮食诱导的大鼠脂肪肝。此外，小檗碱逆转了高脂饮食诱导的非酒精性脂肪性肝病大鼠中MTTP和LDLR的异常表达。目前的研究结果表明，通过逆转MTTP和LDLR的异常表达并抑制脂质合成，小檗碱给药可改善脂肪肝。
