Duan Haoru, Song Shanshan, Li Rui, Hu Suqin, Zhuang Shuting, Liu Shaoyang, Li Xiaolu, Gao Wei
School of Acupuncture - Moxibustion, and Tuina, Beijing University of Chinese Medicine, Beijing, 100029, China.
Department of Acupuncture and Moxibustion, Chaoyang District Traditional Chinese Medicine Hospital, Beijing, 100026, China.
Diabetol Metab Syndr. 2024 Sep 11;16(1):218. doi: 10.1186/s13098-024-01432-7.
Recent studies have highlighted type 2 diabetes (T2DM) as a significant risk factor for the development of metabolic dysfunction-associated fatty liver disease (MAFLD). This investigation aimed to assess electroacupuncture's (EA) impact on liver morphology and function in T2DM rats, furnishing experimental substantiation for its potential to stall MAFLD progression in T2DM.
T2DM rats were induced by a high-fat diet and a single intraperitoneal injection of streptozotocin, and then randomly assigned to five groups: the T2DM group, the electroacupuncture group, the metformin group, combination group of electroacupuncture and metformin, combination group of electroacupuncture and Compound C. The control group received a standard diet alongside intraperitoneal citric acid - sodium citrate solution injections. After a 6-week intervention, the effects of each group on fasting blood glucose, lipids, liver function, morphology, lipid droplet infiltration, and fibrosis were evaluated. Techniques including Western blotting, qPCR, immunohistochemistry, and immunofluorescence were employed to gauge the expression of key molecules in AMPK-associated glycolipid metabolism, insulin signaling, autophagy, and fibrosis pathways. Additionally, transmission electron microscopy facilitated the observation of liver autophagy, lipid droplets, and fibrosis.
Our studies indicated that hyperglycemia, hyperlipidemia and IR promoted lipid accumulation, pathological and functional damage, and resulting in hepatic steatosis and fibrosis. Meanwhile, EA enhanced the activation of AMPK, which in turn improved glycolipid metabolism and autophagy through promoting the expression of PPARα/CPT1A and AMPK/mTOR pathway, inhibiting the expression of SREBP1c, PGC-1α/PCK2 and TGFβ1/Smad2/3 signaling pathway, ultimately exerting its effect on ameliorating hepatic steatosis and fibrosis in T2DM rats. The above effects of EA were consistent with metformin. The combination of EA and metformin had significant advantages in increasing hepatic AMPK expression, improving liver morphology, lipid droplet infiltration, fibrosis, and reducing serum ALT levels. In addition, the ameliorating effects of EA on the progression of MAFLD in T2DM rats were partly disrupted by Compound C, an inhibitor of AMPK.
EA upregulated hepatic AMPK expression, curtailing gluconeogenesis and lipogenesis while boosting fatty acid oxidation and autophagy levels. Consequently, it mitigated blood glucose, lipids, and insulin resistance in T2DM rats, thus impeding liver steatosis and fibrosis progression and retarding MAFLD advancement.
最近的研究强调2型糖尿病（T2DM）是代谢功能障碍相关脂肪性肝病（MAFLD）发生的重要危险因素。本研究旨在评估电针（EA）对T2DM大鼠肝脏形态和功能的影响，为其延缓T2DM中MAFLD进展的潜力提供实验依据。
通过高脂饮食和单次腹腔注射链脲佐菌素诱导T2DM大鼠，然后随机分为五组：T2DM组、电针组、二甲双胍组、电针与二甲双胍联合组、电针与Compound C联合组。对照组接受标准饮食并腹腔注射柠檬酸-柠檬酸钠溶液。经过6周的干预后，评估每组对空腹血糖、血脂、肝功能、形态、脂滴浸润和纤维化的影响。采用蛋白质免疫印迹法、qPCR、免疫组织化学和免疫荧光等技术来检测AMPK相关糖脂代谢、胰岛素信号、自噬和纤维化途径中关键分子的表达。此外，透射电子显微镜有助于观察肝脏自噬、脂滴和纤维化情况。
我们的研究表明，高血糖、高血脂和胰岛素抵抗促进了脂质积累、病理和功能损伤，导致肝脂肪变性和纤维化。同时，电针增强了AMPK的激活，进而通过促进PPARα/CPT1A和AMPK/mTOR途径的表达、抑制SREBP1c、PGC-1α/PCK2和TGFβ1/Smad2/3信号通路的表达来改善糖脂代谢和自噬，最终对改善T2DM大鼠的肝脂肪变性和纤维化发挥作用。电针的上述作用与二甲双胍一致。电针与二甲双胍联合在增加肝脏AMPK表达、改善肝脏形态、脂滴浸润、纤维化以及降低血清ALT水平方面具有显著优势。此外，AMPK抑制剂Compound C部分破坏了电针对T2DM大鼠MAFLD进展的改善作用。
电针上调肝脏AMPK表达，减少糖异生和脂肪生成，同时提高脂肪酸氧化和自噬水平。因此，它减轻了T2DM大鼠的血糖、血脂和胰岛素抵抗，从而阻碍肝脂肪变性和纤维化进展，延缓MAFLD进程。
