三七总皂苷注射液对高脂饮食兔主动脉粥样硬化形成的干预作用

Effects of Panax Notoginseng Saporins Injection on Atherosclerosis Formation of Aortic Artery in Experimental Rabbits

目的:从调节血脂代谢、保护血管内皮细胞分泌功能和改善血管粥样硬化斑块结构等方面探讨三七总皂苷(PNS)注射液防治高脂膳食兔主动脉粥样硬化(AS)的药用效果。方法:将41只新西兰兔随机分为空白对照组(喂食普通颗粒饲料)、AS模型组(喂食高脂颗粒饲料)、PNS灌胃组(高脂颗粒饲料+灌胃PNS粉200 mg·kg-1·d-1)、PNS中、高剂量注射组(高脂颗粒饲料+静脉注射PNS 50、100 mg·kg-1·d-1),最后两组兔在试验过程中的第3~4周,第7~8周及第11~12周期内每天经兔耳静脉注射PNS共计3个疗程。第12周结束时由兔耳缘静脉采血,送检测定内皮素-1(ET-1)、血栓素(TXB2)、6-酮-前列环素(6-Keto-PGF1α)、脂质、一氧化氮(NO)及一氧化氮合酶(NOS)活性,观察兔主动脉壁及其粥样硬化斑块病理结构变化。结果:静脉注射PNS高、中剂量组及灌胃组与AS组比较,血脂各项指标显著改善,ET-1、TXB2显著减少;NO、6-keto-PGF1a及NOS活性显著升高。病理学:各PNS干预组与AS组相比较,兔主动脉内膜粥样斑块面积减少、粥样斑块厚度变薄;泡沫细胞数量明显减少,平滑肌细胞的增生、迁移受到抑制,血管内皮细胞胞浆内小脂质空泡减少,以及各种细胞器完整,偶见到中层平滑肌细胞质脂类小空泡,内弹力板基本连续完整。结论:静脉注射PNS治疗与其口服治疗效果一样,调节AS异常的血脂和血管内皮细胞分泌的血管活性因子,改善AS异常的血管壁微结构及其超微结构,抑制AS斑块形成。

Objective:To investigate the pharmacological effect and mechanism of Panax notoginsen saponins(PNS)injection for preventing and treating rabbit arteriosclerosis(AS)induced by high-fat forage through observing the related indexes of lipid metabolism,vascular endothelial cell function and plaque structure.Methods:The experimental model of atherosclerosis in rabbits was established by hyper-lipoidal feed with 1.5%cholesterol diet in this study.Forty-one healthy New Zealand rabbits were randomly divided into 5 groups:control group,AS group(untreated cholesterol-fed),oral PNS group which was administered intragastrically with a dose of 200 mg·kg-1·d-1 of PNS powder,medium and high dose PNS injection groups(50 mg·kg-1·d-1,100 mg·kg-1·d-1).In latter two groups,PNS was injected from 3rd to 4th,7th to 8th and 11th to 12th week for two weeks.After the experiment was for 12 consecutive weeks,plasma Endothelin-1(ET-1),thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-Keto-PGF1α),serum lipids,nitrous oxide(NO)and the activity of nitricoxide synthase(NOS)were tested.At the same time,the pathological changes of the aorta and its atheroclerotic plaques were observed.Results:Compared to AS group,the blood lipids in the two PNS injection groups and oral PNS group were obviously improved and the serum levels of ET-1 and TXB2 were obviously reduced(P<0.01).The serum levels of NO and 6-Keto-PGF1αwere higher(P<0.01).The activity of NOS was higher(P<0.01)in high and medium dose PNS groups too.Pathology showed that the two PNS injection groups and oral PNS group decreased the area of atherosclerotic plaque and caused the plaques smaller and thinner.The formation of foam cells,proliferation and migration of smooth muscle cells from media to tunica intima in the plaques of two PNS injection groups and oral PNS group were decreased as compared with those in AS group.No lipid-drop let vacuoles in cytoplasm of the endothelial cells,and various cell organs and elastic membrane were seen,but few lipid drop let vacuoles in cytoplasm of medial smooth muscle cells were found in two PNS injection groups and oral PNS group.The pathological changes in the two PNS injection groups were even lighter than those of the oral PNS group.Conclusion:PNS injection as well as oral adiministration,had certain protective effects on the ultrastructure of vascular endothelial cells and smooth muscle cells,regulating the secration of endothelial cells and lessening the formation of atherosclerotic plaques in AS rabbits.