Department of Gynecology and Obstetrics, The Second Hospital of Nanjing, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing; Department of Gynecology and Obstetrics, 904 Hospital of the People's Liberation Army joint Logistic Support Force, Wuxi.
Department of Gynecology and Obstetrics, 904 Hospital of the People's Liberation Army joint Logistic Support Force, Wuxi.
Eur J Histochem. 2024 Sep 17;68(3):4093. doi: 10.4081/ejh.2024.4093.
This study investigates the effectiveness of Shenlin Baizhu powder in managing non-alcoholic fatty liver disease (NAFLD) during pregnancy and its mechanism through the PI3K/AKT/mTOR signaling pathway. Eight healthy male and 24 female Sprague-Dawley rats were used. After acclimatization, 6 female rats were fed normal chow, and 18 female rats were fed high-fat chow to induce NAFLD. After 8 weeks, female rats were mated with males to create a pregnant NAFLD model. The rats were divided into four groups: normal feeding, high-fat diet with saline, high-fat diet with 1.6 g/kg Shenlin Baizhu powder, and high-fat diet with 4.8 g/kg Shenlin Baizhu powder. Maternal body weight, serum and liver levels of aspartate aminotransferase (AST), alanine transaminase (ALT), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), related inflammatory indexes interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. Liver tissue was examined using hematoxylin and oil red O staining, and protein expression related to the PI3K/AKT/mTOR pathway was assessed via Western blotting, immunohistochemistry and RT-PCR. Results showed significant weight gain and increases in ALT, AST, TG, TC, LDL-C, IL-1β, TNF-α, and IL-6, along with decreased HDL-C in NAFLD rats compared to controls. The high and low-dose Shenlin Baizhu powder groups exhibited improvements in body weight, liver histopathology, and reductions in serum TG, TC, LDL-C, ALT, AST, IL-1β, TNF-α, and IL-6, with increased HDL-C levels. Notably, the high-dose group showed greater efficacy in reducing hepatic fat accumulation, liver function markers, blood lipids, and inflammatory indexes, and decreased expression of hepatic PPARγ mRNA, SREBP1 mRNA, AKT mRNA, and related proteins. Shenlin Baizhu powder demonstrates potential in ameliorating high-fat diet-induced NAFLD in pregnant rats, likely through modulation of the PI3K/AKT/mTOR pathway, suggesting its therapeutic potential for gestational NAFLD.
本研究旨在探讨参苓白术散通过 PI3K/AKT/mTOR 信号通路对妊娠合并非酒精性脂肪性肝病（NAFLD）的治疗效果。实验选用 8 只雄性和 24 只雌性 Sprague-Dawley 大鼠。适应性喂养后，将 6 只雌性大鼠喂以普通饲料，18 只喂以高脂饲料以建立 NAFLD 模型。8 周后，雌性大鼠与雄性大鼠交配以建立妊娠合并 NAFLD 模型。将大鼠分为四组：正常喂养组、高脂饲料+生理盐水组、高脂饲料+1.6g/kg 参苓白术散组和高脂饲料+4.8g/kg 参苓白术散组。测量各组大鼠的体质量、血清及肝组织中天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、相关炎症指标白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。通过苏木精-伊红（HE）染色和油红 O 染色观察肝组织病理学变化，Western blot、免疫组化和 RT-PCR 检测 PI3K/AKT/mTOR 通路相关蛋白的表达。结果显示，与对照组相比，NAFLD 大鼠的体质量显著增加，ALT、AST、TG、TC、LDL-C、IL-1β、TNF-α和 IL-6 水平升高，HDL-C 水平降低。与高脂饲料+生理盐水组相比，参苓白术散高、低剂量组大鼠的体质量、肝组织病理学、血清 TG、TC、LDL-C、ALT、AST、IL-1β、TNF-α和 IL-6 水平降低，HDL-C 水平升高。与低剂量组相比，参苓白术散高剂量组大鼠的肝脂肪堆积、肝功能标志物、血脂和炎症指标改善更明显，肝组织过氧化物酶体增殖物激活受体γ（PPARγ）mRNA、固醇调节元件结合蛋白 1（SREBP1）mRNA、AKT mRNA 及相关蛋白表达降低。参苓白术散可能通过调控 PI3K/AKT/mTOR 信号通路改善妊娠合并 NAFLD 大鼠的病情，具有治疗妊娠期 NAFLD 的潜力。
