Zhong Fang-Wei, Li Geng-Xi, Zeng Li
Basic Medical College, Shaoyang University Shaoyang 422000, China.
Hunan Engineering Research Center of Development and Utilization of Traditional Chinese Medicine in Southwest Hunan, Shaoyang University Shaoyang 422000, China.
Zhongguo Zhong Yao Za Zhi. 2022 May;47(9):2500-2508. doi: 10.19540/j.cnki.cjcmm.20211208.401.
This study aimed to explore the effects of Gynostemma pentaphyllum saponins(GPs) on non-alcoholic fatty liver disease(NAFLD) induced by high-fat diet in rats and reveal the underlying mechanism. The NAFLD model rats were prepared with high-fat diet. Forty male Sprague Dawley(SD) rats were randomly assigned into the control group, model group, and low-, moderate-, and high-dose GPs(50, 100, and 150 mg·kg~(-1), respectively) groups. After intragastric administration for 8 continuous weeks, we determined the body weight, liver weight, the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-c), high-density lipoprotein cholesterol(HDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum, and the levels of TC, TG, malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), and interleukin 6(IL-6) in the liver. Furthermore, we observed the pathological changes of liver tissue by oil red O staining and hematoxylin-eosin(HE) staining, sequenced the 16 S rRNA of the intestinal flora in rat feces, and determined the content of short-chain fatty acids in rat feces. The results showed that GPs inhibited the excessive weight gain of high-fat diet-induced NAFLD in rats, reduced the liver weight, lowered the TC, TG, LDL-c, AST, and ALT levels in serum(P<0.05), and rose the HDL-c level in serum(P<0.01). GPs relieved the liver damage caused by high-fat diet, mainly manifested by the lowered levels of TC, TG, MDA, and IL-6 in the liver(P<0.01) and elevated levels of CAT and SOD in the liver. Furthermore, GPs reversed the intestinal flora disorder caused by high-fat diet, restored the diversity of intestinal flora, increased the relative abundance of Bacteroides, and reduced the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroides. Moreover, GPs promoted the proliferation of beneficial bacteria such as Akkermansia, Bacteroides, and Parabacteroides, and inhibited the growth of harmful bacteria such as Desulfovibrio, Escherichia-Shigella, and Helicobacter. GPs increased the content of short-chain fatty acids(acetic acid, propionic acid, and butyric acid)(P<0.01). These findings indicate that GPs can alleviate the high-fat diet-induced NAFLD in rats via regulating the intestinal flora and short-chain fatty acid metabolism.
本研究旨在探讨绞股蓝皂苷（GPs）对高脂饮食诱导的大鼠非酒精性脂肪性肝病（NAFLD）的影响，并揭示其潜在机制。采用高脂饮食制备NAFLD模型大鼠。将40只雄性Sprague Dawley（SD）大鼠随机分为对照组、模型组以及低、中、高剂量GPs组（分别为50、100和150 mg·kg⁻¹）。连续灌胃8周后，测定大鼠体重、肝脏重量、血清中总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-c）、高密度脂蛋白胆固醇（HDL-c）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平，以及肝脏中TC、TG、丙二醛（MDA）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和白细胞介素6（IL-6）的水平。此外，通过油红O染色和苏木精-伊红（HE）染色观察肝组织的病理变化，对大鼠粪便中的肠道菌群16S rRNA进行测序，并测定大鼠粪便中短链脂肪酸的含量。结果表明，GPs抑制了高脂饮食诱导的NAFLD大鼠体重过度增加，降低了肝脏重量，降低了血清中TC、TG、LDL-c、AST和ALT水平（P<0.05），并提高了血清中HDL-c水平（P<0.01）。GPs减轻了高脂饮食引起的肝脏损伤，主要表现为肝脏中TC、TG、MDA和IL-6水平降低（P<0.01）以及肝脏中CAT和SOD水平升高。此外，GPs逆转了高脂饮食引起的肠道菌群紊乱，恢复了肠道菌群的多样性，增加了拟杆菌属的相对丰度，降低了厚壁菌门的相对丰度以及厚壁菌门与拟杆菌属的比例。而且，GPs促进了诸如阿克曼氏菌、拟杆菌属和副拟杆菌属等有益菌的增殖，并抑制了诸如脱硫弧菌属、埃希氏菌-志贺氏菌属和幽门螺杆菌等有害菌的生长。GPs增加了短链脂肪酸（乙酸、丙酸和丁酸）的含量（P<0.01）。这些研究结果表明，GPs可通过调节肠道菌群和短链脂肪酸代谢减轻高脂饮食诱导的大鼠NAFLD。
