龙生蛭胶囊抑制大鼠动脉粥样硬化形成保护血管内皮功能的分子机制研究  

Protective Effects and Mechanism of Longshengzhi Capsules on Inhibiting Atherosclerosis Formation and Improving Vascular Dysfunction in Rats

作　　者：方欢乐[1] 陈衍斌 张飒乐[1] 马怀芬[1] 贾航欢 赵铭[3] FANG Huanle CHEN Yanbin ZHANG Sale MA Huaifen JIA Hanghuan ZHAO Ming(Medical College of Xi＇an Peihna University, Xi＇an 710125 Shaanxi, China Shanxi Buchang Pharmaceutical Co., Ltd, Xi＇an 710075 Shanxi, China Department of Pharmacology, Xi＇an Jiaotong University Health Science Center, Xi＇an 710061 Shanxi, China)

机构地区：[1]西安培华学院医学院,陕西西安710125 [2]陕西步长制药有限公司科研部,陕西西安710075 [3]西安交通大学医学部,陕西西安710061

出　　处：《中药新药与临床药理》2017年第1期6-13,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金青年基金(81402924);陕西省教育厅科研计划项目(15JK2089);陕西省重点科技创新人才推进计划(2015KCT-19)

摘　　要：目的研究龙生蛭胶囊对动脉粥样硬化(atherosclerosis,AS)大鼠动脉血管内皮的保护作用,并对其作用机理进行初步探讨。方法正常对照组给予普通饲料,其余大鼠连续给予高脂饲料12周,同时于实验开始时1次性腹腔注射维生素D60万IU·kg^(-1)复制AS模型。于开始造模4周后各组大鼠分别灌胃龙生蛭(LSZ)胶囊低、中、高3个剂量(0.72,1.44,2.88 g·kg^(-1)),辛伐他汀5.5 mg·kg^(-1),正常对照组给予等体积生理盐水。采用生物化学法检测血脂总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平及一氧化氮(NO)含量;敏感肌张力描计技术检测动脉血管收缩/舒张功能;Western blot检测内皮型一氧化氮合酶(e NOS)及血管细胞黏附分子^(-1)(VCAM^(-1))的蛋白活性及表达;ELASA测定血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的水平。结果与模型组比较,龙生蛭胶囊中、高剂量组均能降低血液中TC、TG、LDL-C并升高HDL-C,降低血清IL-6、TNF-α水平,增加血清NO含量并提高血管内皮e NOS活性(P<0.05,P<0.01);龙生蛭胶囊高剂量组可明显改善高脂饲料诱导的动脉血管环对苯肾上腺素(PE)和5-羟色氨(5-HT)的收缩反应,及对内皮依赖性舒张剂乙酰胆碱(ACh)的舒张反应,并且舒张作用可被N-硝基-L-精氨酸甲酯(L-NAME)阻断(P<0.05,P<0.01)。实验结果还发现龙生蛭胶囊中、高剂量组均能降低由高脂诱导的VCAM^(-1)表达升高(P<0.05,P<0.01)。结论龙生蛭胶囊可显著性降低AS大鼠血脂水平;改善大鼠血管内皮依赖性血管舒张功能;抑制系统炎性反应,其机制可能与上调e NOS活性、抑制VCAM^(-1)表达相关。表明龙生蛭胶囊不仅可用于防治脑梗的发生,还对AS早期病变具有良好的治疗作用。Objective To research the inhibitory effects of Longshengzhi Capsules（LSZ） on high-fat-induced atherosclerosis（AS） formation in rats,and to explore its protective mechanism on improving vascular dysfunction.Methods The rat hyperlipidemia model was set up by feeding high-fat food for 12 weeks and by injection with one-dose vitamin D（600 000 U·kg-1）intraperitoneally. Four weeks after injection,the rats of medication groups were treated with LSZ（0.72,1.44,2.88 g·kg-1）or Simvastatin（5.5 mg·kg-1）orally,and the model group was administrated same volume of solvent. Biochemical methods were used to detect serum levels of cholesterol（TC）,triglyceride（TG）,low-density lipoprotein cholesterol（LDL-C）,high-density lipoprotein cholesterol（HDL-C）and nitric oxide（NO）. The changes in isometric tension of isolated arterial rings were recorded continuously by a myograph system. Endothelial nitric oxide synthase（e NOS）and vascular cell adhesion molecule 1（VCAM-1）protein expression and activities were detected by Western blot. The levels of serum interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were measured by enzyme-linked immunosorbent assay（ELISA） kit. Results Compared with the AS model group,LSZ（1.44 and 2.88 g·kg-1） decreased the serum levels of TC,TG,LDL-C,IL-6 and TNF-α,increased the serum HDL-C level and the NO content,and up-regulated the vascular e NOS activity（P〈0.05,P〈0.01）. We also found that LSZ（2.88 g·kg-1） obviously decreased the contraction reaction of high-fat-feeding rat isolated arterial rings to phenylephrine（PE）and 5-hydroxytryptamine（5-HT）,and improved the maximum endothelial relaxation induced by acetylcholine（ACh）,whereas the beneficial effects of LSZ could be attenuated by N-nitro-L-arginine methyl ester（L-NAME）（P〈0.05,P〈0.01）. In addition,LSZ（1.44 and 2.88 g·kg-1）significantly inhibited vascular VCAM-1protein expression of hyperlipidemia rats（P〈0.05,P〈0.01）. Conclusion LSZ could dec

关 键 词：龙生蛭胶囊 动脉粥样硬化 血管功能 内皮依赖性舒张 系统炎性反应 

分 类 号：R285.5[医药卫生—中药学]