Alternative and Complementary Medicine for Gastrointestinal and Liver Diseases Research Unit, Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
BMC Complement Med Ther. 2020 Jun 1;20(1):162. doi: 10.1186/s12906-020-02962-z.
The prevalence of nonalcoholic steatohepatitis (NASH) in menopausal women is increasing, but current treatments have not been proven effective. The objective of this study was to investigate the treatment effects of genistein and running exercise in ovariectomized (OVX) rats with NASH.
Thirty-six female Sprague-Dawley rats were divided into 6 groups, control; OVX with standard diet; OVX with high fat and high fructose (HFHF) diet for 4 weeks; OVX with HFHF and genistein treatment (16 mg/kg BW/day) for 5 weeks (OVX + HFHF+GEN); OVX with HFHF and moderate intensity exercise for 5 weeks (OVX + HFHF+EX); OVX with HFHF and combined treatments (OVX + HFHF+GEN + EX). Serum interleukin-6 (IL-6) levels, hepatic free fatty acid (FFA), hepatic glutathione (GSH), and hepatic malondialdehyde (MDA) levels were measured. Liver histology was examined to determine NASH severity.
OVX + HFHF group had the highest levels of hepatic FFA compared with OVX and control groups (5.92 ± 0.84 vs. 0.37 ± 0.01 vs. 0.42 ± 0.04 nmol/mg protein, respectively, p < 0.01). Serum IL-6 levels were significantly elevated in both OVX and OVX + HFHF groups as compared with controls (112.13 ± 6.50 vs. 121.47 ± 3.96 vs. 86.13 ± 2.40 pg/mL, respectively, p < 0.01). In OVX + HFHF group, hepatic MDA levels were higher, while GSH levels were lower than in OVX and control groups (MDA; 0.98 ± 0.04 vs. 0.82 ± 0.02 vs. 0.78 ± 0.03 nmol/mg protein, and GSH; 46.01 ± 0.91 vs. 55.21 ± 1.40 vs. 57.94 ± 0.32, respectively; p < 0.01 for both). Comparing with OVX + HFHF group, rats that received genistein, exercise and combined treatments demonstrated an improvement in liver histopathology, decreased levels of hepatic FFA (1.44 ± 0.21 vs. 0.45 ± 0.04 vs. 0.49 ± 0.05 nmol/mg protein, respectively, p < 0.01), serum IL-6 (82.80 ± 2.07 vs. 83.47 ± 2.81 vs. 94.13 ± 1.61 pg/mL, respectively, p < 0.01), and hepatic MDA (0.80 ± 0.03 vs. 0.76 ± 0.02 vs. 0.76 ± 0.03 nmol/mg protein, respectively, p < 0.01).
Genistein and moderate intensity exercise were effective in reducing the severity of NASH in OVX rats through the reduction in liver inflammation, oxidative stress and liver fat contents.
绝经后妇女非酒精性脂肪性肝炎(NASH)的患病率正在上升,但目前的治疗方法尚未被证明有效。本研究旨在探讨染料木黄酮和跑步运动对 NASH 去卵巢(OVX)大鼠的治疗作用。
36 只雌性 Sprague-Dawley 大鼠分为 6 组,分别为对照组;标准饮食的 OVX 组;高脂高果糖(HFHF)饮食 4 周的 OVX 组;HFHF 和染料木黄酮治疗(16mg/kgBW/天)5 周的 OVX 组(OVX+HFHF+GEN);HFHF 和中等强度运动 5 周的 OVX 组(OVX+HFHF+EX);HFHF 和联合治疗的 OVX 组(OVX+HFHF+GEN+EX)。测量血清白细胞介素-6(IL-6)水平、肝游离脂肪酸(FFA)、肝谷胱甘肽(GSH)和肝丙二醛(MDA)水平。检查肝组织病理学以确定 NASH 严重程度。
与 OVX 和对照组相比,OVX+HFHF 组的肝 FFA 水平最高(分别为 5.92±0.84、0.37±0.01 和 0.42±0.04 nmol/mg 蛋白,p<0.01)。与对照组相比,OVX 和 OVX+HFHF 组的血清 IL-6 水平均显著升高(分别为 112.13±6.50、121.47±3.96 和 86.13±2.40 pg/mL,p<0.01)。在 OVX+HFHF 组中,肝 MDA 水平升高,而 GSH 水平降低,与 OVX 和对照组相比(MDA;0.98±0.04、0.82±0.02 和 0.78±0.03 nmol/mg 蛋白,GSH;46.01±0.91、55.21±1.40 和 57.94±0.32,分别;p<0.01)。与 OVX+HFHF 组相比,接受染料木黄酮、运动和联合治疗的大鼠肝组织病理学改善,肝 FFA 水平降低(分别为 1.44±0.21、0.45±0.04 和 0.49±0.05 nmol/mg 蛋白,p<0.01),血清 IL-6(分别为 82.80±2.07、83.47±2.81 和 94.13±1.61 pg/mL,p<0.01)和肝 MDA(分别为 0.80±0.03、0.76±0.02 和 0.76±0.03 nmol/mg 蛋白,p<0.01)。
染料木黄酮和中等强度运动通过减少肝脏炎症、氧化应激和肝脏脂肪含量,有效减轻 OVX 大鼠 NASH 的严重程度。