基于PI3K/AKT/mTOR信号通路的神灵白术散对妊娠合并非酒精性脂肪肝发病机制的研究

IF 2.1 4区 生物学 Q4 CELL BIOLOGY European Journal of Histochemistry Pub Date : 2024-09-17 DOI:10.4081/ejh.2024.4093
Yao Le,Zhijun Wang,Qian Zhang,Ling Miao,Xiaohong Wang,Guorong Han
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引用次数: 0

摘要

本研究通过PI3K/AKT/mTOR信号通路,探讨了神林白术粉治疗妊娠期非酒精性脂肪肝(NAFLD)的有效性及其机制。采用 8 只健康雄性大鼠和 24 只雌性 Sprague-Dawley 大鼠。适应环境后,6 只雌性大鼠喂食正常饲料,18 只雌性大鼠喂食高脂肪饲料以诱导非酒精性脂肪肝。8 周后,雌性大鼠与雄性大鼠交配,建立妊娠非酒精性脂肪肝模型。大鼠分为四组:正常喂养组、高脂饮食加生理盐水组、高脂饮食加每公斤 1.6 克神灵白术粉组和高脂饮食加每公斤 4.8 克神灵白术粉组。母体体重、血清和肝脏中的天门冬氨酸氨基转移酶(AST)、丙氨酸转氨酶(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(LDL-C)、高密度脂蛋白胆固醇(LDL-C)和低密度脂蛋白胆固醇(LDL-C)的水平、高密度脂蛋白胆固醇(HDL-C)、相关炎症指标白细胞介素-1 β(IL-1 β)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)。使用苏木精和油红 O 染色检查肝组织,并通过 Western 印迹、免疫组化和 RT-PCR 评估与 PI3K/AKT/mTOR 通路相关的蛋白质表达。结果显示,与对照组相比,非酒精性脂肪肝大鼠体重明显增加,ALT、AST、TG、TC、LDL-C、IL-1β、TNF-α和IL-6升高,HDL-C降低。神林白术粉高剂量组和低剂量组的体重、肝脏组织病理学均有所改善,血清 TG、TC、LDL-C、ALT、AST、IL-1β、TNF-α 和 IL-6 均有所下降,HDL-C 水平有所升高。值得注意的是,大剂量组在减少肝脏脂肪堆积、肝功能指标、血脂和炎症指标方面表现出更大的疗效,并降低了肝脏 PPARγ mRNA、SREBP1 mRNA、AKT mRNA 和相关蛋白的表达。神林白术粉可能通过调节PI3K/AKT/mTOR通路,具有改善高脂饮食诱导的妊娠大鼠非酒精性脂肪肝的潜力,这表明它具有治疗妊娠期非酒精性脂肪肝的潜力。
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Study on the mechanism of Shenling Baizhu powder on the pathogenesis of pregnancy complicated with non-alcoholic fatty liver, based on PI3K/AKT/mTOR signal pathway.
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.
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来源期刊
European Journal of Histochemistry
European Journal of Histochemistry 生物-细胞生物学
CiteScore
3.70
自引率
5.00%
发文量
47
审稿时长
3 months
期刊介绍: The Journal publishes original papers concerning investigations by histochemical and immunohistochemical methods, and performed with the aid of light, super-resolution and electron microscopy, cytometry and imaging techniques. Coverage extends to: functional cell and tissue biology in animals and plants; cell differentiation and death; cell-cell interaction and molecular trafficking; biology of cell development and senescence; nerve and muscle cell biology; cellular basis of diseases. The histochemical approach is nowadays essentially aimed at locating molecules in the very place where they exert their biological roles, and at describing dynamically specific chemical activities in living cells. Basic research on cell functional organization is essential for understanding the mechanisms underlying major biological processes such as differentiation, the control of tissue homeostasis, and the regulation of normal and tumor cell growth. Even more than in the past, the European Journal of Histochemistry, as a journal of functional cytology, represents the venue where cell scientists may present and discuss their original results, technical improvements and theories.
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