海带多糖对高脂饮食性大鼠主动脉一氧化氮合酶和细胞外基质的调节作用  

Laminaria japonica polysaccharides rebalances the expressions of eNOS,iNOS,MMP-2 and MMP-9 in aorta of rats with hyperlipidemia induced by high fat diet

作　　者：倪华[1] 方田[1] 陈向凡[1] 

机构地区：[1]南通大学附属医院药剂科,南通大学药学院,南通226001

出　　处：《中药药理与临床》2016年第6期97-101,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：南通大学校级基金项目(03041172)

摘　　要：目的:观察海带多糖对高脂饮食性大鼠主动脉内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)与基质金属蛋白酶(MMP)-2、MMP-9表达的影响,探讨海带多糖抗高脂饮食诱导血管病变的作用与机制。方法:采用高脂饲料联合维生素D3诱导大鼠高脂血症。造模成功后,将大鼠随机分为正常组、模型组、辛伐他汀2 mg/kg、海带多糖低剂量(250 mg/kg)、中剂量(500 mg/kg)、高剂量(1000 mg/kg)治疗组。给药8周后,颈动脉取血测定血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)的含量;测定血清与主动脉中NO和一氧化氮合酶(NOS)的含量。取大鼠主动脉,蛋白免疫印迹法检测eNOS、iNOS、MMP-2和MMP-9的蛋白表达,RT-PCR法分析eNOS、iNOS与MMP-2、MMP-9的基因表达。结果:与模型组相比,海带多糖在1000 mg/kg剂量下能显著降低血清中TC、TG、LDL-C的含量,同时也可升高HDL-C的含量;在500 mg/kg剂量下能够降低TG的含量,提高HDL-C的含量。海带多糖治疗能够显著恢复高脂饮食性引起的血清和主动脉NO和NOS含量的降低。此外,海带多糖在1000 mg/kg剂量下能显著抑制主动脉iNOS与MMP-2、MMP-9的表达,上调eNOS的蛋白表达;在500 mg/kg剂量下能明显降低血管iNOS并升高eNOS的表达。结论:海带多糖除改善高脂饮食性血清脂质谱,提高血清和大动脉NO及NOS含量外,对高脂饮食性大鼠主动脉eNOS、iNOS与MMP-2、MMP-9表达有再平衡作用。Objective： To observe the effects of Laminaria Japonica Polysaccharides （LJP） on the expressions of endothelial nitric oxide synthase （eNOS） , inducible nitric oxide synthase （iNOS） , matrix metalloproteinase 2 （MMP-2） , and MMP-9 in aorta in rats with hyperlipidemia in- duced by high fat diet. Methods： The study explored the rat with hyperlipidemia made by administration of high fat diet plus vitamin D3. After hyperlipidemia, rats were randomly assigned to normal group, model group, positive control group, LJP treatment groups （250,500, and 1000 mg/kg/d, respectively）. After 8 weeks of treatment, the blood was taken via carotid artery, the content of serum total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDL-C）, and high density lipoprotein cholesterol （HDL-C）, and to detect the content of nitric oxide （NO） and nitric oxide synthase enzyme （NOS） in the serum and aorta were determined. Western blot was used to detect the protein expression of eNOS, iNOS and MMP-2 and MMP-9. RT-PCR assay was used to determine the mRNA expression of eNOS, iNOS, MMP-2, and MMP-9. Results： High fat diet induced the hyperlioidemia and up-regulated the expression of iNOS, MMP2, and MM9 in both mRNA and protein level in rat aorta, but levels of eNOS in both protein and mRNA reduced. While HJP improved the serum lipid profile, LJP at 500 and 1000 mg/kg significantly reduced the contents of TC, TG, LDL-C, but increased the content of HDL-C in serum. LJP recovered the reduced content of NO and NOS in serum and in aorta. LJP at 500 and 1000 mg/kg significantly suppressed the expression of aortic iNOS, MMP-2 and MMP-9 ,respectively. However, LJP at 1000 mg/kg increased the mRNA and protein expression of eNOS. Conclusions ： LJP improved the serum lipid profile, recovered the reduced NO and NOS in serum and aorta, and re-balanced the expression of iNOS, eNOS, MMP2 and MMP9 in aorta in rats with hyperlipidemia, respectively.

关 键 词：海带多糖 动脉粥样硬化 内皮型一氧化氮合酶 诱导型一氧化氮合酶 基质金属蛋白酶 

分 类 号：R285.5[医药卫生—中药学]