芝麻素对大鼠非酒精性脂肪性肝病的预防作用

【作者】 代利；

【导师】 倪淑华；

【作者基本信息】 山西医科大学 ， 营养与食品卫生学， 2011， 硕士

【摘要】 目的:用高脂膳食诱发大鼠脂肪肝模型,观察芝麻素对大鼠实验性非酒精性脂肪肝的预防作用并探讨其作用机制。方法:健康雄性SD大鼠40只以普通饲料适应性喂养3天后,按体重及初始胆固醇水平随机分为5组,正常对照组、高脂模型组、芝麻素低、中、高剂量组(低、中、高剂量分别为20、40、80mg/kg·d^-1)。9周后放血处死动物,测血清及肝匀浆中总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、、超氧化物岐化酶（SOD）、丙二醛（MDA）;血丙氨酸氨基转移酶（ALT）门冬氨酸氨基转移酶（AST）及肝匀浆脂蛋白脂酶（LPL）、肝脂酶（HL）活力。逆转录PCR检测肝组织胆固醇7α羟化酶（CYP7A1）及肝细胞色素P450（CYP）2E1mRNA表达水平变化;肝组织切片观察肝脏病理改变。结果:1.高脂模型组肝指数明显高于正常对照组（P﹤0.05）,芝麻素各剂量组肝指数较高脂模型组低（P﹤0.05）,但三个剂量组之间无差异。2.高脂模型组血清TC明显高于正常对照组（P﹤0.05）,芝麻素中、高剂量组TC低于高脂模型组（P﹤0.01）;各组大鼠TG无显著性差异（P﹥0.05）;高脂模型组HDL-C低于正常对照组,芝麻素各剂量组HDL-C明显高于高脂模型组（P﹤0.01）;高脂模型组LDL-C高于正常对照组（P﹤0.05）,芝麻素各剂量组LDL-C低于高脂模型组（P﹤0.01）。3.高脂模型组较正常对照组肝匀浆TC、TG、LDL-C均升高（P<0.05）;芝麻素三个剂量组较高脂模型组TC、TG、LDL-C均下降（P<0.05）。随芝麻素剂量增加TC、TG、LDL-C含量逐渐下降（P<0.05）4.高脂模型组LPL、ALT活性低于正常对照组,芝麻素高剂量组较高脂对照组LPL、ALT活性增高（P<0.05）,其余各组间无统计学差异;各组间HL,AST无统计学差异。5.高脂模型组血清及肝脏FFA含量高于正常对照组（P<0.05）,芝麻素各剂量组FFA含量均低于高脂模型组（P<0.05）,但各剂量组间无统计学差异。6.高脂模型组、正常对照组及芝麻素各剂量组血清SOD无明显差异。高脂模型组较正常对照组肝匀浆SOD活力有所下降（P<0.01）,芝麻素各剂量组SOD活力较高脂模型组均升高（P<0.01）,且随芝麻素剂量增加SOD活力增加。高脂模型组血清及肝匀浆MDA含量较正常对照组高（P<0.01）;芝麻素各剂量组MDA含量均低于高脂模型组（P<0.01）,芝麻素各剂量组间差异无统计学意义。7.与正常组相比,高脂模型组CYP7A1mRNA表达水平显著下降（P<0.05）,芝麻素各组CYP7A1mRNA表达水平明显高于高脂模型组（P<0.05）。与正常组相比,高脂模型组CYP2E1mRNA表达水平显著增加（P<0.05）,芝麻素各组CYP2E1mRNA表达水平明显低于高脂模型组（P<0.05）。8.光镜观察下观察可见:正常对照组肝小叶结构完整、清晰,中央静脉大而壁薄,肝细胞排列成肝索,在中央静脉周围呈放射状排列;模型组大鼠肝组织见重度脂肪变,肝细胞体积增大,排列紊乱,索状结构不清,细胞内充满以大空泡为主的混合性空泡,部分伴肝细胞水样变,细胞核被挤向包膜,部分细胞核溶解,并伴炎细胞浸润;各芝麻素组脂肪变性肝细胞数量及程度明显较模型组轻,肝细胞肿胀不明显,细胞内脂滴较高脂组少,脂肪变以小泡性为主,细胞核居中,未见炎性细胞浸润。脂肪变细胞数量明显增多,无明显炎性细胞浸润。结论:芝麻素能降低脂肪肝大鼠肝中脂质的含量,阻碍了初次打击对脂肪肝形成的作用;同时能显著增强SOD活性,减少氧化代谢产物MDA含量,显著降低CYP2E1mRNA的表达,因而能从提高机体抗氧化的能力,以及抑制CYP2E1mRNA表达方面阻断第二次打击对肝细胞脂肪病变的进展。因而对非酒精性脂肪肝有一定的预防作用。更多还原

【Abstract】 Objective To study whether sesamin can prevent the development ofrats’nonalcoholic fatty liver disease.Methods 40 SD rats were randomly divided into 5 groups according tothe initial serum cholesterol and weight．The normal control group，model group，and three doses of seamine groups(20、40、80mg/kg·d^-1)．After 9 weeks，TC，TG，LDL，HDL in liver and sera were determined by biochemistry analysis，andthe malondialdehyde（MDA） and superoxidedismutase（SOD） activity of hepatictissue and sera were measured．FFA, AST, ALT in sera and LPL,HL in liver werealso measured．The expression levels of cholesterol 7αhydroxylase （CYP7A1） andCytochrome P4502E1 mRNA in liver tissue were measured by reversetranscriptase-polymerase chain reaction （RT-PCR）．The liver pathology wasobserved under the light microscope．Results1. Liver/body weight index of model group was increased significantly comparedwith normal group（P﹤0.05）.Compared with model group ,the treatment groupswere decreased markedly（P﹤0.05）.2. TC in sera of model group was increased significantly compared with normalgroup（P﹤0.05）. Compared with model group, the middle and high dosestreatment groups were decreased markedly（P﹤0.05）.TG had no significantdifferences. HDL in sera of model group was decreased significantly comparedwith normal group（P﹤0.05）. Compared with model group, the treatmentgroups were increased markedly（P﹤0.05）. LDL in sera of model group wasincreased significantly compared with normal group（P﹤0.05）. Compared withmodel group, the treatment groups were decreased markedly（P﹤0.05）3. TC,TG,LDL in liver of model group were increased significantly compared withnormal group（P﹤0.05,）. Compared with model group, the treatment groupswere decreased markedly（P﹤0.05）4. LPL and ALT in liver of model group were decreased significantly comparedwith normal group（P﹤0.05）. Compared with model group, the high dosetreatment group were decreased markedly（P﹤0.05）. HL and AST had nosignificant differences.5. FFAs in both sera and liver of model groups were increased significantly compared with normal group（P﹤0.05）. Compared with model group, thetreatment groups were decreased markedly（P﹤0.05）6. SOD in sera had no significant differences. SOD in liver of model group wasdecreased significantly compared with normal group（P﹤0.01）. Compared withmodel group, the treatment groups were increased markedly（P﹤0.01）. MDA insera and liver of model group was increased significantly compared withnormal group（P﹤0.05）. Compared with model group, the treatment groupswere decreased markedly（P﹤0.05）.7. The expression of CYP7A1 mRNA in model group was decreased significantlycompared with that of normal group（P<0.05）.Compared with model group, thetreatment groups were increased remarkably（P﹤0.05）.The expression ofCYP2E1 mRNA in model group was increased significantly compared with thatof normal group（P<0.05）. Compared with model group, the treatment groupswere decreased remarkably（P﹤0.05）.8. Pathology observed by HE stain: Steatosis was not seen in controlled group,while severe lipid degeneration of liver were found in model group. Comparedwith model group, lipid degeneration in treatment groups were decreasedremarkably.Conclusions Sesamin can decrease fat in liver, increase the activity ofSOD, and decrease MDA and the expression of CYP2E1. So, sesamin can preventthe development of rats＇nonalcoholic fatty liver disease.更多还原