Seif El-Din Sayed H, El-Lakkany Naglaa M, El-Naggar Abeer A, Hammam Olfat A, Abd El-Latif Hekma A, Ain-Shoka Afaf A, Ebeid Fatma A
Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt.
Department of Pathology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza 12411, Egypt.
Res Pharm Sci. 2015 Jul-Aug;10(4):275-87.
The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased, especially in patients exhibit one or more features of the metabolic syndrome. This study investigates the effect of rosuvastatin (RSV) and/or β-carotene (βC) in NAFLD-induced rats. Rats were classified into nine groups; normal (I), NAFLD-induced with high-fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with RSV (IV, V), βC (VI, VII) or both RSV+βC (VIII, IX), respectively. After four weeks, rats were sacrificed to obtain serum samples and liver tissues. Liver histology, lipid profile, liver oxidative stress markers, and adipocytokines were measured. Liver sections of rats with NAFLD-HFD revealed steatosis, lose of hepatic architecture, inflammation and hepatocyte vacuolation with high percentage of cell fibrosis. Serum levels of ALT, AST, ALP, gamma glutamyl transferase (GGT) and lipid profile (triglycerides, cholesterol, LDL and VLDL) were significantly increased (P<0.05) compared with normal. Also, hepatic malondialdehyde level and serum leptin, tumor necrosis factor-alpha (TNF-α) and transforming growth factor-β1 (TGF-β1) were increased. Meanwhile, superoxide dismutase (SOD) activity, GSH content in liver, serum HDL and adiponectin were decreased (P<0.05) vs normal. These changes were observed to a lesser extent in NAFLD-RD group. Administration of RSV or/and βC almost improved all previously mentioned parameters. Moreover, hepatic steatosis was decreased and inflammation was markedly ameliorated with reduction of TNF-α and TGF-β. These results were more pronounced in the groups VIII and IX vs each drug alone. In conclusion RSV and βC could be beneficial for the treatment and prevention of NAFLD. Combined RSV with βC is more effective than RSV alone.
非酒精性脂肪性肝病（NAFLD）的患病率显著增加，尤其是在具有一种或多种代谢综合征特征的患者中。本研究调查了瑞舒伐他汀（RSV）和/或β-胡萝卜素（βC）对NAFLD诱导大鼠的影响。大鼠被分为九组：正常组（I）、高脂饮食诱导的NAFLD组（HFD；II）、转为常规饮食的NAFLD组（RD；III）、NAFLD-HFD或NAFLD-RD分别用RSV治疗组（IV，V）、βC治疗组（VI，VII）或RSV+βC联合治疗组（VIII，IX）。四周后，处死大鼠以获取血清样本和肝脏组织。测量肝脏组织学、血脂谱、肝脏氧化应激标志物和脂肪细胞因子。NAFLD-HFD大鼠的肝脏切片显示脂肪变性、肝结构丧失、炎症和肝细胞空泡化，伴有高比例的细胞纤维化。与正常组相比，血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（ALP）、γ-谷氨酰转移酶（GGT）水平和血脂谱（甘油三酯、胆固醇、低密度脂蛋白和极低密度脂蛋白）显著升高（P<0.05）。此外，肝脏丙二醛水平以及血清瘦素、肿瘤坏死因子-α（TNF-α）和转化生长因子-β1（TGF-β1）升高。同时，超氧化物歧化酶（SOD）活性、肝脏中谷胱甘肽（GSH）含量、血清高密度脂蛋白（HDL）和脂联素降低（P<0.05），与正常组相比。在NAFLD-RD组中，这些变化程度较轻。给予RSV或/和βC几乎改善了所有上述参数。此外，肝脏脂肪变性减轻，炎症明显改善，TNF-α和TGF-β降低。这些结果在VIII组和IX组中比单独使用每种药物时更明显。总之，RSV和βC可能对NAFLD的治疗和预防有益。RSV与βC联合使用比单独使用RSV更有效。
