基于氧化应激反应探讨绞股蓝皂苷对高脂血症豚鼠肝脏损伤的保护作用

戴天艺; 刘冬恋; 秦兴敏; 高成玲; 李佳乙; 邝海玲

doi:10.13386/j.issn1002-0306.2024020003

基于氧化应激反应探讨绞股蓝皂苷对高脂血症豚鼠肝脏损伤的保护作用

Protective Effects of Gynostemma pentaphyllum Saponins on Liver Injury in Guinea Pigs of Hyperlipemia Based on Oxidative Stress

摘要

摘要: 目的：从氧化应激角度探讨绞股蓝皂苷（Gynostemma pentaphyllum saponins，GPs）对高脂血症模型豚鼠肝脏损伤的保护作用。方法：将32只豚鼠随机分为模型组、GPs低剂量组（85 mg/kg）、GPs高剂量组（170 mg/kg）和辛伐他汀组（1.5 mg/kg），每组8只。采用高脂饲料喂养5周，制备高脂血症模型。同时将8只豚鼠设立为正常组，给予普通饲料。从第6周开始，造模同时灌胃给药，正常组和模型组给予等量生理盐水，每日给药1次，连续4周。每周测量各组豚鼠的体质量、体长，并计算Lee's 指数。实验结束时，测定豚鼠血清中脂质（TC、TG、HDL和LDL）水平；豚鼠肝质量、肝体比与空腹血糖；肝脏中氧化应激（SOD、MDA、CAT和GSH-px）水平；采用HE和油红O染色观察豚鼠肝脏组织的形态；采用免疫荧光方法观察豚鼠肝脏Nrf2和HO-1的蛋白表达。结果：实验结束时，与模型组比较，GPs高、低剂量组豚鼠的体质量均极显著降低（P<0.01）。GPs低剂量组Lee's指数显著降低（P<0.05）；GPs高剂量组Lee's指数极显著降低（P<0.01）。GPs低剂量组血清中TG和LDL水平均显著降低（P<0.05，<0.01）；GPs高剂量组血清中TC、TG和LDL水平均显著降低（P<0.05，<0.01）。GPs低剂量组肝组织中MDA水平显著下降（P<0.05）；GPs高剂量组肝组织中SOD水平显著上升（P<0.05），MDA水平极显著下降（P<0.01）。病理观察发现，GPs高剂量组可缓解肝脏的脂肪变性，减少脂滴聚集。GPs高、低剂量组Nrf2和HO-1蛋白的荧光表达均增强（P<0.01）。结论：GPs可通过激活肝脏的Nrf2/HO-1信号通路改善高脂血症豚鼠肝脏的氧化应激水平，从而改善高脂血症导致的豚鼠肝脏损伤。

Abstract: Objective: To observe the protective effects of Gynostemma pentaphyllum saponins (GPs) on liver injury in guinea pigs of hyperlipemia based on oxidative stress. Methods: A total of 32 guinea pigs were randomly divided into a model group, a low dose GPs group (85 mg/kg), a high dose GPs group (170 mg/kg), and a simvastatin group (1.5mg/kg), with 8 animals in each group. All animals were fed with high-fat diet for 5 weeks to prepare a hyperlipemia model. At the same time, 8 guinea pigs were set up as a normal group and given regular feed. From the 6 th week onwards, hyperlipemia model guinea pigs were fed with high-fat diet go on, and were given intragastric administration at the same time, once a day for 4 consecutive weeks. The normal group and model group were given equal amount of normal saline. The body mass, body length, and Lee's index of each group of guinea pigs were measured weekly. After the experiment, the levels of total TC, TG, HDL and LDL of guinea pigs were measured. The liver mass, liver to body ratio, and fasting blood glucose of guinea pigs were measured. The levels of SOD, MDA, CAT and GSH-px in the liver were detected. HE and oil red staining were used to observe the pathological and morphological changes of guinea pig liver tissue. Immunofluorescence method was used to observe the protein expression of Nrf2 and HO-1 in the liver of guinea pigs. Results: At the end of the experiment, compared with the model group, the low dose and high dose group of GPs significantly decreased the level of the body mass (P<0.01) in hyperlipidemic guinea pigs. The low dose group of GPs significantly decreased the Lee's index (P<0.05); the Lee's index in The high dose group of GPs significantly decreased the Lee's index (P<0.01). The low dose group of GPs significantly decreased the levels of TG and LDL in serum (P<0.05, P<0.01). The high dose group of GPs significantly decreased the levels of TC, TG, and LDL in serum (P<0.05, P<0.01). The low dose group of GPs significantly decreased the level of MDA in the liver tissue (P<0.05). The high dose group of GPs significantly increased the level of SOD (P<0.05), and decreased the level of MDA (P<0.01) in the liver tissue. Pathology showed that the high dose group of GPs reduced the fatty degeneration and lipid droplet accumulation in the hepatocytes of hyperlipidemic guinea pigs. The fluorescence expression of Nrf2 and HO-1 proteins in both the high and low dose groups of GPs significantly increased (P<0.01). Conclusion: GPs would have a good hepatic protective effect through significantly improve oxidative stress levels by activate the Nrf2/HO-1 signaling pathway in guinea pigs of hyperlipemia.