论文部分内容阅读
【目的】观察荔枝核有效部位群(SLEC)对大鼠非酒精性脂肪肝(NAFLD)的治疗作用,并探讨其作用机制。【方法】选用SPF级大鼠,雌雄各半,采用高脂饲料加高脂乳液灌胃8周复制NAFLD模型,造模成功后将造模组大鼠根据体质量和血糖值随机分为模型组、SLEC低剂量组(剂量为0.74 g·kg-1·d-1)、SLEC高剂量组(剂量为1.48 g·kg-1·d-1)和二甲双胍组(剂量为100 mg·kg-1·d-1),每组8只,雌雄各半,并设正常组为对照。给药4周后,腹主动脉采血、取肝组织。采用全自动生化分析仪检测血清甘油三酯(TG)、胆固醇(CHOL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、空腹血糖(FBG);采用比色法检测血清游离脂肪酸(NEFA)、放射免疫法检测血清胰岛素(Ins)含量,计算稳态模型胰岛素抵抗指数(HOMA-IR)、胰岛素敏感性指数(ISI);采用甘油磷酸氧化酶—过氧化物酶偶联(GPO-PAP)法、胆固醇氧化酶—过氧化物酶偶联(COD-PAP)法、水溶性四氮唑(WST-1)法、硫代巴比妥酸(TBA)法分别检测肝组织TG、CHOL、超氧化物歧化酶(SOD)和丙二醛(MDA)含量;观察大鼠肝脏组织病理变化,采用实时荧光定量PCR和Western-blot法分别检测大鼠肝组织固醇调节元件结合蛋白-1c(SREBP-1c)m RNA和蛋白的表达。【结果】SLEC高剂量组能显著降低NAFLD大鼠血清TG、LDL-C、NEFA和肝脂质含量,提高大鼠血清SOD含量,明显改善大鼠HOMA-IR、提高ISI,与模型组比较差异均有统计学意义(P<0.05),且SLEC高剂量组改善肝细胞脂质沉积作用明显。与模型组比较,SLEC高、低剂量均能显著降低大鼠肝组织SREBP-1c m RNA及蛋白表达(P<0.05)。【结论】SLEC对NAFLD大鼠肝细胞脂质沉积的病理状况具有明显改善作用,作用机制与调节脂质代谢、降低NEFA水平,改善IR、抗氧化应激和下调SREBP-1c基因与蛋白表达有关。
【Objective】 To observe the therapeutic effect of effective fractions of litchi nucleus (SLEC) on non-alcoholic fatty liver disease (NAFLD) in rats and its mechanism of action. 【Methods】 SPF rats were randomly divided into male and female rats. The NAFLD model was induced by intragastric administration of high-fat diet plus high-fat emulsion for 8 weeks. After successful model establishment, rats in model group were randomly divided into model group , SLEC low dose group (0.74 g · kg-1 · d-1), SLEC high dose group (1.48 g · kg-1 · d-1) and metformin group · D-1), each group of 8, male and female, and set the normal group as a control. After 4 weeks of administration, blood was taken from the abdominal aorta and liver tissues were taken. The contents of serum triglyceride (TG), cholesterol (CHOL), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT) (AST) and fasting blood glucose (FBG). Serum free fatty acid (NEFA) was detected by colorimetric method. Serum insulin level was measured by radioimmunoassay. HOMA-IR and insulin sensitivity (GPI-PAP), cholesterol oxidase-peroxidase coupling (COD-PAP), water-soluble tetrazolium (WST-1) ) And thiobarbituric acid (TBA) were used to detect the contents of TG, CHOL, SOD and MDA in liver tissue. The pathological changes of liver tissues were observed by real-time fluorescence quantitative PCR and Western-blot were used to detect the expression of SREBP-1c mRNA and protein in rat liver tissue. [Results] The high dose SLEC group could significantly reduce the levels of serum TG, LDL-C, NEFA and hepatic lipid in NAFLD rats, increase the level of SOD in serum, significantly improve HOMA-IR and increase ISI in rats (P <0.05), and the effect of SLEC high dose group on hepatocyte lipid deposition was obvious. Compared with the model group, high and low dose of SLEC could significantly reduce the SREBP-1c mRNA and protein expression in rat liver tissue (P <0.05). 【Conclusion】 SLEC has a significant effect on the pathological changes of lipid deposition in hepatic cells of NAFLD rats. The mechanism is related to the regulation of lipid metabolism, the decrease of NEFA, the improvement of IR, antioxidant stress and down-regulation of SREBP-1c gene and protein expression .