洋甘菊总黄酮对高脂血症模型小鼠脂质代谢的影响及机制
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篇名: 洋甘菊总黄酮对高脂血症模型小鼠脂质代谢的影响及机制
TITLE: Effects of Total Flavonoids from Chamomile on Lipid Metabolism of Hyperlipidemia Model Mice and Its Mechanism
摘要: 目的:研究洋甘菊总黄酮对高脂血症模型小鼠脂质代谢的影响及潜在机制。方法:将30只雄性载脂蛋白E基因缺陷(C57BL/6J-ApoE-/-)小鼠随机分成模型组、阳性对照组(非诺贝特30mg/kg)和洋甘菊总黄酮低、中、高剂量组(88、176、352mg/kg),每组6只;另取6只雄性C57BL/6J小鼠作为正常对照组。正常对照组小鼠用普通饲料喂养,其余各组小鼠均用高脂饲料喂养8周以复制高脂血症模型。造模同时,各给药组小鼠灌胃相应药液(均以1%羧甲基纤维素钠溶液为溶剂),正常对照组和模型组小鼠灌胃1%羧甲基纤维素钠溶液,每次灌胃200μL,每天1次,连续8周。分别于给药前和给药8周后称定各组小鼠的体质量,测定末次给药后小鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)含量,肝组织中超氧化物歧化酶(SOD)、丙二醛(MDA)含量以及过氧化物酶体增殖物激活受体α(PPARα)、肉毒碱棕榈酰基转移酶1A(CPT1A)、过氧化物酶酰基辅酶A氧化酶1(ACOX1)蛋白的表达水平,并观察肝组织的病理改变。结果:与给药前比较,各组小鼠给药8周后的体质量均有升高趋势。与正常对照组比较,模型组小鼠给药8周后的体质量和血清中TC、TG、LDL-C、AST、ALT含量以及肝组织中MDA含量均显著升高(P<0.05或P<0.01),血清中HDL-C含量和肝组织中SOD含量以及PPARα、CPT1A、ACOX1蛋白的表达水平均显著降低(P<0.05或P<0.01),肝组织结构紊乱并可见大小不一的圆形脂肪空泡,细胞质中可见大小不等的脂滴。与模型组比较,洋甘菊总黄酮各剂量组和阳性对照组小鼠给药8周后的体质量(除洋甘菊总黄酮低剂量组外)和血清中TC、TG、LDL-C、AST、ALT含量以及肝组织中MDA(除洋甘菊总黄酮低、中剂量组外)含量均显著降低(P<0.05或P<0.01),血清中HDL-C含量和肝组织中SOD含量以及PPARα、CPT1A(除洋甘菊总黄酮低、中剂量组外)、ACOX1蛋白的表达水平均显著升高(P<0.05或P<0.01),肝组织结构较清晰,肝脏脂肪空泡有不同程度的改善,脂滴变少,其中洋甘菊总黄酮高剂量组小鼠上述指标的改善效果最好。结论:洋甘菊总黄酮可预防C57BL/6J-ApoE-/-小鼠高脂血症的发生,其机制可能与上调PPARα表达、改善肝损伤和氧化应激损伤有关。
ABSTRACT: OBJECTIVE:To st udy t he effects of total flavonoids from chamomile on lipid metabolism of hyperlipidemia model mice and its potential mechanism. METHODS :Thirty male C 57BL/6J-ApoE-/- mice were randomly divided into model group , positive control group(fenofibrate 30 mg/kg)and chamomile total flavonoids low-dose ,medium-dose and high-dose groups (88, 176,352 mg/kg),with 6 mice in each group. In addition ,6 male C 57BL/6J mice were used as normal control group. Mice in normal control group were fed with ordinary diet ,and mice in other groups were fed with high-fat diet for 8 weeks to replicate hyperlipidemia model. At the time of making model ,administration groups were given relevant liquid (using 1% sodium carboxymethyl cellulose as solvent );normal control group and model group were given 1% sodium carboxymethyl cellulose intragastrically,200 mL per gavage ,once a day ,for consecutive 8 weeks. The body weight of mice in each group was weighed before medication and 8 weeks after medication. The serum contents of total cholesterol (TC),triacylglycerol(TG),low-density lipoprotein cholesterol (LDL-C),high-density lipoprotein cholesterol (HDL-C),aspartate aminotransferase (AST)and alanine aminotransferase (ALT) in mice were detected after last administration ;the contents of superoxide dismutase (SOD) and malondialdehyde(MDA)as well as the protein expressions of peroxisome proliferator-activated receptor α(PPARα),carnitine palmityl transferase 1A(CPT1A)and peroxase acyl-CoA oxidase 1(ACOX1)in liver tissue were determined. The pathological changes i n liver tissue were observed. RESULTS:Compared w ith before medication ,the body weight of each group showed an increasing trend after 8 weeks of medication. Compared with normal control group ,body weight ,the contents of TC ,TG, LDL-C,AST and ALT in serum and MDA content in live r lan- tissue of mice in model group were significantly increased wei516@sina.com after 8 weeks of medication (P<0.05 or P<0.01). The ·2706· China Pharmacy content of HDL-C in serum and the cont ent of SOD in liver tissue ,as well as the protein expressions of PPARα,CPT1A and ACOX1 were significantly decreased (P<0.05 or P<0.01),and the structure of liver tissue was disorganized ,with circular fat vacuoles of different sizes and lipid droplets of different sizes in the cytoplasm. Compared with model group ,body weight (except for chamomile total flavonoids low-dose group )of mice ,serum contents of TC ,TG,LDL-C,AST and ALT ,content of MDA in liver tissue (except for chamomile total flavonoids low-dose and medium-dose groups )were significantly decreased (P<0.05 or P< 0.01). Serum content of HDL-C ,content of SOD in liver tissue ,protein expressions of PPARα,CPT1A(except for chamomile total flavonoids low-dose and medium-dose groups ) and ACOX 1 were significantly increased (P<0.05 or P<0.01);liver tissue structure was clear ,and liver fat vacuoles were improved to varying degrees ,and less lipid droplets. The improvement effect of the above indexes was the best in the chamomile total flavonoids high-dose group. CONCLUSIONS :Chamomile total flavonoids can prevent the occurrence of hyperlipidemia in C57BL/6J-ApoE -/- mice,the mechanism of which may be associated with up-regulation of PPARα expression,the improvement of liver injury and oxidant stress injury.
期刊: 2021年第32卷第22期
作者: 兰卫
AUTHORS: LAN Wei
关键字: 洋甘菊总黄酮;高脂血症;载脂蛋白E基因缺陷小鼠;脂质代谢;作用机制
KEYWORDS: Total flavonoids from chamomile ;Hyperlipidemia;C57BL/6J-ApoE-/- mice;Lipid metabolism ;Mechanism of
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