Effect of Danzhi Tiaozhi Decoction on the PI3K/AKT/FOXO1 Signaling Pathway in High-Fat Induced MAFLD Rats
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摘要:
目的 研究丹栀调脂汤对高脂饮食诱导的代谢相关脂肪性肝病(MAFLD)大鼠PI3K/AKT/FOXO1信号通路的影响, 探讨其在MAFLD治疗中的作用。 方法 雄性SD大鼠分为正常组、模型组及丹栀调脂汤高、中、低剂量组。正常组和模型组予等体积的生理盐水, 丹栀调脂汤高、中、低剂量组分别予丹栀调脂汤20.4、10.2、5.1 g·kg-1·d-1, 连续灌胃8周后取材。检测5组大鼠体质量、血脂、血糖、胰岛素水平及HOMA-IR变化情况; 肝脏组织脂质沉积情况; Western blot检测PI3K/AKT信号通路中各蛋白表达水平。 结果 与正常组比较, 模型组大鼠体质量、TG、TC、FFA、GLU、INS、LDL-C及HOMA-IR水平明显升高, HDL-C水平明显降低; 肝脏组织油红O染色可见明显肿大的肝细胞及明显的脂质沉积; PI3K、AKT蛋白磷酸化表达水平显著降低。相较于模型组, 丹栀调脂汤高、中、低剂量组体质量、TG、TC、FFA、GLU、INS、LDL-C及HOMA-IR水平不同程度降低; 肝细胞肿大、肝细胞脂滴及排列结构均有不同程度的改善; PI3K、AKT、FOXO1蛋白磷酸化表达水平升高。 结论 丹栀调脂汤可能通过PI3K/AKT/FOXO1信号通路改善胰岛素抵抗, 进而达到防治MAFLD的目的。 -
关键词:
- 丹栀调脂汤 /
- 代谢相关脂肪性肝病 /
- PI3K/AKT/FOXO1信号通路
Abstract:OBJECTIVE To study the effect of Danzhi Tiaozhi Decoction on the PI3K/AKT/FOXO1 signaling pathway in rats with high-fat-diet (HFD) induced metabolic associated fatty liver disease (MAFLD), and to explore its role in the treatment of MAFLD. METHODS Male SD rats were divided into the normal group, HFD model group, and high, medium, and low dose groups of Danzhi Tiaozhi Decoction. The normal group and HFD group were given equal volumes of saline, while the high, medium, and low dose groups of Danzhi Tiaozhi Decoction were given Danzhi Tiaozhi Decoction 20.4, 10.2, and 5.1 g · kg-1·d-1, respectively. The samples were collected after 8 weeks of continuous gavage. Detect the changes in body mass, blood lipids, blood glucose, insulin levels, HOMA-IR, and liver tissue lipid deposition in the five groups of rats. Western blot was used to detect the expression levels of proteins in the PI3K/AKT signaling pathway. RESULTS Compared with the normal group, the body mass, TG, TC, FFA, GLU, INS, LDL-C, and HOMA-IR levels of the HFD model group rats were significantly increased, while the HDL-C levels were significantly reduced; oil red O staining of liver tissue reveals obvious enlargement of liver cells and significant lipid deposition; the phosphorylation expression levels of PI3K and AKT proteins were significantly reduced. Compared with the HFD group, the body mass, TG, TC, FFA, GLU, INS, LDL-C, and HOMA-IR levels of the high, medium, and low dose groups of Danzhi Tiaozhi Decoction were significantly declined; the enlarged liver cells, lipid droplets and arrangement structure of liver cells were improved to varying degrees; the phosphorylation expression levels of PI3K and AKT proteins were increased. CONCLUSION Danzhi Tiaozhi Decoction may improve insulin resistance through the PI3K/AKT/FOXO1 signaling pathway, thereby achieving the goal of preventing and treating MAFLD. -
图 1 高脂饮食诱导对大鼠体质量及代谢指标的影响
注: Control.正常组(n=6);HFD.模型组(n=24)。与Control组比较, ##P < 0.01。x±s。
Figure 1. Effect of HFD induction on body mass and metabolic indicators in rats
图 2 丹栀调脂汤对高脂大鼠体质量、GLU、INS水平及HOMA-IR的影响
注: Control.正常组; HFD.模型组; L-DZTZ.丹栀调脂汤低剂量组; M-DZTZ.丹栀调脂汤中剂量组; H-DZTZ.丹栀调脂汤高剂量组。与Control组比较, ##P < 0.01, ###P < 0.001;与HFD组比较, *P < 0.05, **P < 0.01, ***P < 0.001。x±s，n=6。
Figure 2. Effect of Danzhi Tiaozhi Decoction on body mass, blood sugar, insulin levels, and HOMA-IR in HFD rats
图 3 丹栀调脂汤对高脂大鼠肝功能、血脂及FFA的影响
注: Control.正常组; HFD.模型组; L-DZTZ.丹栀调脂汤低剂量组; M-DZTZ.丹栀调脂汤中剂量组; H-DZTZ.丹栀调脂汤高剂量组。与Control组比较, ##P < 0.01;与HFD组比较, *P < 0.05, **P < 0.01。x±s，n=6。
Figure 3. Effect of Danzhi Tiaozhi Decoction on liver function, blood lipids, and FFA in HFD rats
图 4 丹栀调脂汤对高脂大鼠肝脏组织的病理学影响(油红O, ×100)
注: Control.正常组; HFD.模型组; L-DZTZ.丹栀调脂汤低剂量组; M-DZTZ.丹栀调脂汤中剂量组; H-DZTZ.丹栀调脂汤高剂量组
Figure 4. Pathological effects of Danzhi Tiaozhi Decoction on liver tissue of HFD rats (Oil Red O, × 100)
图 5 丹栀调脂汤对高脂大鼠肝脏中TG、TC的影响
注: Control.正常组; HFD.模型组; L-DZTZ.丹栀调脂汤低剂量组; M-DZTZ.丹栀调脂汤中剂量组; H-DZTZ.丹栀调脂汤高剂量组。与Control组比较, ##P < 0.01;与HFD组比较, *P < 0.05, **P < 0.01。x±s，n=6。
Figure 5. Effect of Danzhi Tiaozhi Decoction on TG and TC in the liver of HFD rats
图 6 丹栀调脂汤对高脂大鼠PI3K/AKT/FOXO1信号通路相关蛋白表达的影响
注: Control.正常组; HFD.模型组; L-DZTZ.丹栀调脂汤低剂量组; M-DZTZ.丹栀调脂汤中剂量组; H-DZTZ.丹栀调脂汤高剂量组。与Control组比较, ##P < 0.01;与HFD组比较, **P < 0.01。x±s，n=6。
Figure 6. Effect of Danzhi Tiaozhi Decoction on the expression of PI3K/AKT/FOXO1 signaling pathway related proteins in HFD rats
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