本文選題：荔枝核有效部位群　切入點：非酒精性脂肪肝　出處：《廣州中醫(yī)藥大學(xué)》2016年碩士論文

【摘要】：目的：通過高脂飲食8周建立非酒精性脂肪肝合并胰島素抵抗(NAFLD-IR)大鼠模型,研究荔枝核有效部位群(Semen Litchi Effective Constituents,SLEC)(含皂苷、黃酮、鞣質(zhì))對該病理模型的藥理作用和作用機(jī)制,進(jìn)一步探究該有效部位群具有的降脂、降糖作用以及其作用機(jī)制。方法：將90只SPF級SD大鼠(雌性45只、雄性45只),根據(jù)體重隨機(jī)分為正常組8只、造模組82只,采用高脂飼料加高脂乳液灌胃8周的方法建立NAFLD-IR模型,模型建立后將造模組大鼠根據(jù)體重、空腹血糖(FBG)或2h血糖值隨機(jī)分為模型組、SLEC低劑量組(074g·kg-1·d-1)、SLEC高劑量組(1.48g·kg-1·d-1)、二甲雙胍組(100mg·kg-1·d-1),每組8只,雌雄各半。灌胃給藥4周后,腹主動脈采血、取肝組織。檢測血清甘油三酯(TG)、膽固醇(CHOL)、高密度脂蛋白膽固醇(HDL-C)低密度脂蛋白膽固醇(LDL-C)、谷丙轉(zhuǎn)氨酶(ALT)、谷草轉(zhuǎn)氨酶(AST)、空腹血糖(FBG),用比色法檢測血清游離脂肪酸(NEFA)含量,放射免疫法測定血清胰島素(Ins)含量并計算穩(wěn)態(tài)模型胰島素抵抗指數(shù)HOMA-IR、胰島素敏感性指數(shù)ISI,采用甘油磷酸氧化酶—過氧化物酶偶聯(lián)(GPO-PAP)法、膽固醇氧化酶—過氧化物酶偶聯(lián)(COD-PAP)法、水溶性四氮唑(WST-1)法、硫代巴比妥酸(TBA)法分別檢測肝組織TG、CHOL、超氧化物歧化酶(SOD)和丙二醛(MDA)含量,采用HE染色和油紅0染色肝組織切片觀察大鼠肝臟病理變化,采用實時熒光定量PCR和western-blot方法分別檢測各組大鼠肝組織SREBP-lc mRNA和SREBP-lc蛋白的相對表達(dá)量。結(jié)果：SLEC低劑量能顯著降低NAFLD-IR大鼠血清NEFA、HOMA-IR、肝脂質(zhì)(P0.05),改善肝細(xì)胞脂質(zhì)貯積病理狀態(tài)；SLEC高劑量能顯著降低NAFLD-IR大鼠血清TG、LDL-C、 HOMA-IR、NEFA和肝脂質(zhì)(P0.05),提高ISI、SOD含量(P0.05),改善肝細(xì)胞脂質(zhì)蓄積病理變性,下調(diào)肝組織SREBP-1c mRNA及蛋白的表達(dá)(P0.05)。結(jié)論：SLEC對NAFLD-IR大鼠高血脂、胰島素抵抗、氧化應(yīng)激及肝細(xì)胞脂質(zhì)蓄積的病理狀況均有明顯改善作用,其機(jī)制與下調(diào)SREBP-1c mRNA及蛋白表達(dá)量有關(guān)。
[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.
【學(xué)位授予單位】：廣州中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R259

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