荔枝核有效部位群对实验性非酒精性脂肪肝的治疗作用和机制研究

发布时间：2018-04-08 22:39

本文选题：荔枝核有效部位群　切入点：非酒精性脂肪肝　出处：《广州中医药大学》2016年硕士论文

【摘要】：目的：通过高脂饮食8周建立非酒精性脂肪肝合并胰岛素抵抗(NAFLD-IR)大鼠模型,研究荔枝核有效部位群(Semen Litchi Effective Constituents,SLEC)(含皂苷、黄酮、鞣质)对该病理模型的药理作用和作用机制,进一步探究该有效部位群具有的降脂、降糖作用以及其作用机制。方法：将90只SPF级SD大鼠(雌性45只、雄性45只),根据体重随机分为正常组8只、造模组82只,采用高脂饲料加高脂乳液灌胃8周的方法建立NAFLD-IR模型,模型建立后将造模组大鼠根据体重、空腹血糖(FBG)或2h血糖值随机分为模型组、SLEC低剂量组(074g·kg-1·d-1)、SLEC高剂量组(1.48g·kg-1·d-1)、二甲双胍组(100mg·kg-1·d-1),每组8只,雌雄各半。灌胃给药4周后,腹主动脉采血、取肝组织。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),用比色法检测血清游离脂肪酸(NEFA)含量,放射免疫法测定血清胰岛素(Ins)含量并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,采用HE染色和油红0染色肝组织切片观察大鼠肝脏病理变化,采用实时荧光定量PCR和western-blot方法分别检测各组大鼠肝组织SREBP-lc mRNA和SREBP-lc蛋白的相对表达量。结果：SLEC低剂量能显著降低NAFLD-IR大鼠血清NEFA、HOMA-IR、肝脂质(P0.05),改善肝细胞脂质贮积病理状态；SLEC高剂量能显著降低NAFLD-IR大鼠血清TG、LDL-C、 HOMA-IR、NEFA和肝脂质(P0.05),提高ISI、SOD含量(P0.05),改善肝细胞脂质蓄积病理变性,下调肝组织SREBP-1c mRNA及蛋白的表达(P0.05)。结论：SLEC对NAFLD-IR大鼠高血脂、胰岛素抵抗、氧化应激及肝细胞脂质蓄积的病理状况均有明显改善作用,其机制与下调SREBP-1c mRNA及蛋白表达量有关。
[Abstract]:To further explore the effective fraction group has the effect of reducing blood lipid, hypoglycemia and its mechanism.Methods: 90 SPF SD rats (45 female and 45 male) were randomly divided into normal group (n = 8) and model group (n = 82) according to their body weight. The NAFLD-IR model was established by gastric perfusion with high fat diet plus high fat emulsion for 8 weeks.After the establishment of the model, the rats in the model group were randomly divided into two groups according to their body weight, fasting blood glucose (FBG) or blood glucose (2h). The rats in the model group were randomly divided into two groups: model group, low dose group (0.74 g kg-1 d-1), high dose group (1.48 g kg-1 d-1), metformin group (100 mg kg-1 d-1), 8 rats in each group, half female and half male.After 4 weeks of intragastric administration, blood was collected from abdominal aorta and liver tissue was taken.Serum triglyceride (TGN), cholesterol (Choll), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), alanine aminotransferase (alt), aspartate aminotransferase (AST), fasting blood glucose (FBGG), and serum free fatty acid (NEFAs) were detected by colorimetry.Serum insulin Ins was measured by radioimmunoassay and insulin resistance index (HOMA-IRI) and insulin sensitivity index (ISI) were calculated in steady-state model. Glycerophosphate oxidase coupled with peroxidase (GPO-PAPs) and cholesterol oxidase-peroxidase coupling assay (COD-PAPP) were used.The contents of TGG Choll, superoxide dismutase (SOD) and malondialdehyde (MDAA) in liver tissue were detected by water soluble tetrazolium tetrazolium (WST-1) and thiobarbituric acid (TBAA) methods respectively. The pathological changes of rat liver were observed by HE staining and oil red 0 staining.The relative expression of SREBP-lc mRNA and SREBP-lc protein were detected by real-time quantitative PCR and western-blot.Results the low dose of NAFLD-IR could significantly decrease the serum NEFA-HOMA-IRand liver lipid P0.05N, improve the pathological state of hepatic cell lipid accumulation. The high dose of SLEC could significantly decrease the serum TGG-LDL-C, HOMA-IRNFA and liver lipid P0.05N, increase the content of ISISOD, improve the pathological degeneration of hepatic cell lipid accumulation, and improve the pathological degeneration of hepatic cell lipid accumulation.The expression of SREBP-1c mRNA and protein in liver tissue was down-regulated (P 0.05).Conclusion the effects of w / w SLEC on hyperlipidemia, insulin resistance, oxidative stress and hepatocyte lipid accumulation in NAFLD-IR rats were significantly improved, and the mechanism was related to the down-regulation of SREBP-1c mRNA and protein expression.
【学位授予单位】：广州中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R259

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