动脉粥样硬化与Insig-2基因的关系及小檗碱的干预作用研究
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摘要
目的
研究小檗碱对家兔高脂模型脂代谢及动脉粥样硬化形成的影响,并探讨其可能作用的机制。
方法
1.采用高脂饮食喂养诱导家兔形成高脂血症和动脉粥样硬化,并用小檗碱进行干预。
2.采用全自动生化分析仪测定各组血清TC、TG、LDL-C、HDL-C、apoA1水平。
3.采用HE染色法观察主动脉病理形态的改变。
4.采用紫外分光光度法测定主动脉中iNOS的活力。
5.采用实时荧光RT-PCR法测定家兔脂肪及肝脏组织中Insig-2、PPARγ、SR-B1 mRNA表达水平。
结果
1.高脂组TC、TG和LDL-C水平较普食组明显升高(P<0.01),而小檗碱干预能明显阻遏高脂饲料喂养所致的血清TC、TG和LDL-C的升高;
2.动脉大体照片和切片可见模型组较正常组主动脉内壁出现大量动脉粥样硬化斑块,并有泡沫样细胞形成。小檗碱干预明显减轻血管内壁动脉粥样硬化程度,减少泡沫样细胞沉积;
3.模型组较正常组iNOS活性显著升高(P<0.01),小檗碱干预能显著抑制高脂饮食诱导的iNOS活性增高(P<0.01);
4.模型组Insig-2 mRNA表达较正常组显著升高(P<0.01),小檗碱干预明显上调Insig-2 mRNA表达(P<0.01);
5.模型组PPARγmRNA表达较正常组显著升高(P<0.01),小檗碱干预显著下调PPARγmRNA表达(P<0.01);
6.模型组SR-B1 mRNA表达较正常组显著升高(P<0.01),小檗碱处理明显下调SR-B1 mRNA表达(P<0.01)。
结论
小檗碱具有明显的降血脂和抗动脉粥样硬化作用,其作用机制至少与上调Insig-2及下调PPARγ、SR-B1基因表达相关。
Objective
To investigate the effects of berberine on lipid metabolism and atherosclerosis and its possible mechanism in rabbits with hyperlipidemia.
Method
1. Hyperlipidemia and atherosclerosis were induced in rabbits by high fat diet and intervention effects of berberine were observed.
2. The serum TC, TG, LDL-C, HDL-C, and apoA1 levels were determined by automatic biochemical analyzer.
3. Slices and HE staining were taken to observe the aortic pathological changes.
4. The activity of inducible nitric oxide synthase (iNOS) from aorta was tested by ultraviolet spectrophotometry.
5. Real-time fluorescent RT-PCR method was used for the determination of Insig-2, PPARγ, and SR-B1 mRNA expressions from fat and liver tissues of rabbits.
Results
1. TC, TG, and LDL-C levels were significantly increased in HFD group, compared with that of normal diet group (P <0.01), and berberine treatment significantly inhibited elevation of serum TC, TG, and LDL-C caused by high fat diet(P <0.01);
2. Photos and slices of arota showed that large amount of atherosclerotic plaque and formation of foam cells in model group, which could be obviously blocked by berberine treatment;
3. A higher iNOS activity was observed in model group, compared with normal group (P <0.01), which could be decreased by berberine treatment (P <0.01);
4. There existed a high mRNA expression of Insig-2 gene in model group and berberine treatment significantly increased the expression ;
5. PPARγmRNA expression in model group was significantly higher than that of normal group (P <0.01), which was down regulated by berberine treatment;
6. SR-B1 mRNA expression was significantly higher in model group than that of normal group (P<0.01) and berberine treatment obviously blunted the increase (P <0.01).
Conclusion
Berberine has obvious hypolipidemic and anti-atherosclerotic effects, its mechanism may be related to increasing expressions of insig-2 genes, and reducing PPARγand SR-B1 gene expression.
研究小檗碱对家兔高脂模型脂代谢及动脉粥样硬化形成的影响,并探讨其可能作用的机制。
方法
1.采用高脂饮食喂养诱导家兔形成高脂血症和动脉粥样硬化,并用小檗碱进行干预。
2.采用全自动生化分析仪测定各组血清TC、TG、LDL-C、HDL-C、apoA1水平。
3.采用HE染色法观察主动脉病理形态的改变。
4.采用紫外分光光度法测定主动脉中iNOS的活力。
5.采用实时荧光RT-PCR法测定家兔脂肪及肝脏组织中Insig-2、PPARγ、SR-B1 mRNA表达水平。
结果
1.高脂组TC、TG和LDL-C水平较普食组明显升高(P<0.01),而小檗碱干预能明显阻遏高脂饲料喂养所致的血清TC、TG和LDL-C的升高;
2.动脉大体照片和切片可见模型组较正常组主动脉内壁出现大量动脉粥样硬化斑块,并有泡沫样细胞形成。小檗碱干预明显减轻血管内壁动脉粥样硬化程度,减少泡沫样细胞沉积;
3.模型组较正常组iNOS活性显著升高(P<0.01),小檗碱干预能显著抑制高脂饮食诱导的iNOS活性增高(P<0.01);
4.模型组Insig-2 mRNA表达较正常组显著升高(P<0.01),小檗碱干预明显上调Insig-2 mRNA表达(P<0.01);
5.模型组PPARγmRNA表达较正常组显著升高(P<0.01),小檗碱干预显著下调PPARγmRNA表达(P<0.01);
6.模型组SR-B1 mRNA表达较正常组显著升高(P<0.01),小檗碱处理明显下调SR-B1 mRNA表达(P<0.01)。
结论
小檗碱具有明显的降血脂和抗动脉粥样硬化作用,其作用机制至少与上调Insig-2及下调PPARγ、SR-B1基因表达相关。
Objective
To investigate the effects of berberine on lipid metabolism and atherosclerosis and its possible mechanism in rabbits with hyperlipidemia.
Method
1. Hyperlipidemia and atherosclerosis were induced in rabbits by high fat diet and intervention effects of berberine were observed.
2. The serum TC, TG, LDL-C, HDL-C, and apoA1 levels were determined by automatic biochemical analyzer.
3. Slices and HE staining were taken to observe the aortic pathological changes.
4. The activity of inducible nitric oxide synthase (iNOS) from aorta was tested by ultraviolet spectrophotometry.
5. Real-time fluorescent RT-PCR method was used for the determination of Insig-2, PPARγ, and SR-B1 mRNA expressions from fat and liver tissues of rabbits.
Results
1. TC, TG, and LDL-C levels were significantly increased in HFD group, compared with that of normal diet group (P <0.01), and berberine treatment significantly inhibited elevation of serum TC, TG, and LDL-C caused by high fat diet(P <0.01);
2. Photos and slices of arota showed that large amount of atherosclerotic plaque and formation of foam cells in model group, which could be obviously blocked by berberine treatment;
3. A higher iNOS activity was observed in model group, compared with normal group (P <0.01), which could be decreased by berberine treatment (P <0.01);
4. There existed a high mRNA expression of Insig-2 gene in model group and berberine treatment significantly increased the expression ;
5. PPARγmRNA expression in model group was significantly higher than that of normal group (P <0.01), which was down regulated by berberine treatment;
6. SR-B1 mRNA expression was significantly higher in model group than that of normal group (P<0.01) and berberine treatment obviously blunted the increase (P <0.01).
Conclusion
Berberine has obvious hypolipidemic and anti-atherosclerotic effects, its mechanism may be related to increasing expressions of insig-2 genes, and reducing PPARγand SR-B1 gene expression.
引文
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