目的 探讨雪胆总皂苷对新西兰兔动脉粥样硬化模型(AS)的影响及其作用机制。方法 将36只雄性新西兰兔随机分为6组,即对照组,模型组,雪胆总皂苷高、中、低剂量(200、100、50 mg/kg)组及阳性药辛伐他汀(200 mg/kg)组。除对照组饲以普通饲料外,其余各组饲以配方高脂饲料(79.5%基础饲料+15%蛋黄粉+5%猪油+0.5%胆固醇)3周,再去除配方高脂饲料中胆固醇继续饲养3周。从造模开始ig给药,每日1次,连续给药6周。给药3周后检测血清三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C);第6周末次给药后检测血清TG、TC、HDL-C、LDL-C、载脂蛋白AI(ApoAI)、载脂蛋白B(ApoB)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮(NO)、内皮素(ET)、血栓素B₂(TXB₂)、肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、白细胞介素6(IL-6)、白细胞介素8(IL-8)和6酮前列腺素F_1α(6-keto-PGF_1α)的量及血液流变学相关指标;计算主动脉脂质面积百分比,并在光镜下观察血管内膜形态学病理改变。结果 与模型组比较,雪胆总皂苷高、中剂量组在给药3周后能明显降低AS兔的血清TC和TG值,其中高剂量组能明显升高血清HDL-C值;雪胆总皂苷高剂量组6周后能明显升高HDL-C、ApoAI、SOD、GSH-Px、NO、6-keto-PGF_1α和降低TC、TG和LDL-C、ApoB、ET、TXB₂、TNF-α、CRP、IL-6和IL-8的量,中、低剂量组以上指标也有不同程度的升高或降低;雪胆总皂苷高、中剂量组能明显降低AS兔的全血黏度(高切和低切)、红细胞聚集指数和主动脉脂质面积百分比,明显改善血管内膜管壁脂质沉积、管壁增厚及管腔狭窄程度。结论 雪胆总皂苷能干预兔AS的发生、发展,其作用环节与调节血脂水平、抗炎作用、保护血管内皮细胞功能和改善血液流变学指标密切相关。

Objective To investigate the anti-atherogenic effects and possible mechanisms of the total saponins from Hemsleya chinensis(TSHC) on New Zealand rabbits with atherosclerosis(AS).Methods Thirty-six male New Zealand rabbits were randomly divided into six groups, namely control, model, TSHC 200, 100, 50 mg/kg, and simvastatin 200 mg/kg groups.In addition to control group fed with normal diet, the rest rabbits of other groups were given fat diet(79.5% basic feed+15% yolk powder+5% lard+0.5% cholesterol) for three weeks, then removed cholesterol, continued to raise for three weeks, starting from modeling gavage once daily for six weeks.The serum triglyceride(TG), total cholesterol(TC), high density lipoprotein-cholesterol(HDL-C), and low density lipoprotein-cholesterol(LDL-C) were detected in the third week;After administration of the sixth week, serum was analyzed for levels of TG, TC, HDL-C, LDL-C, apolipoprotein AI(ApoAI), apolipoprotein B(ApoB), superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px), nitric oxide(NO), endothelin(ET), thromboxane B₂(TXB₂), tumor necrosis factor-α(TNF-α), C-reactive protein(CRP), interleukin-6(IL-6), interleukin-8(IL-8), 6-ketone prostaglandin F_1α(6-keto-PGF_1α), and related parameters of blood rheology;Calculation of aorta lipid area percentage, and pathological changes were observed under light microscopy.Results Compared with the model group, high-and mid-dose TSHC could significantly reduce the contents of TC and TG in the third week;high-dose TSHC could significantly raise the levels of HDL-C, ApoAI, SOD, GSH-Px, NO, and 6-keto-PGF_1α, while lower TC, TG, LDL-C, ApoB, ET, TXB₂, TNF-α, CRP, IL-6, and IL-8, the above indicators in mid-and low-dose groups also have varying degrees of rise and fall;High-dose TSHC could significantly reduce the blood viscosity(high shear and low shear), erythrocyte aggregation index, and the percentage of aortic lipid area, significantly improve vascular intima wall lipid deposition and wall thickening and luminal stenosis degree.Conclusion TSHC could inhibit the development of AS in rabbits, which might be due to adjusting blood lipid levels, anti-inflammatory effects, protecting vascular endothelial cell function, and improving the blood rheology.

重庆市科委重点项目(cstc2012pt-kyys10004,cstc2013jcsf0118);重庆市科委一般项目(cstc2013jcyjA1078)