炎症诱导的新型大鼠动脉粥样硬化模型的建立及Rb1的防治作用

目的通过激发大鼠炎症反应建立新型动脉粥样硬化（AS）动物模型并观察人参皂苷Rb1的抗AS作用。方法模型组采用酵母多糖混悬液（20 mg/kg）每隔3d腹腔注射一次,引发大鼠持续性炎症;相同方法注射无菌石蜡液作为对照组;Rb1组同时腹腔注射Rb1（40 mg/kg）;所有大鼠均喂食高脂饲料,实验共10周。分别通过苏丹染色、透射电镜、real time PCR、免疫组化、ELISA观察大鼠主动脉壁大体标本、超微结构、NFκB、TNFα、IL6的表达。结果模型组可见红染的脂纹、斑块形成,电镜显示内膜下层出现吞噬脂滴的泡沫细胞,NFκB/P65高表达于主动脉壁的内膜层,TNFα、IL6水平均明显高于对照组,经Rb1干预后大体标本可见AS病变明显减轻,电镜下未见泡沫细胞,NFκB、TNFα、IL6水平均较模型组显著降低。结论在高脂喂饲的基础上持续炎症刺激能够成功诱导大鼠AS模型,人参皂苷Rb1能够通过抑制炎症反应抗AS。

A novel rat model of atherosclerosis induced by inflammation and the therapeutic effect of Rb1

Objective To establish a novel atherosclerosis model by inflammation in rats and investigate the antiatherosclerotic effect of Rb1.Methods Healthy male SD rats were randomly divided into three groups, namely the control group, model group （using zymosan A to induce inflammation） and Rb1-treated group （12 rats in each group）.The rats were administered liquid paraffin （i.p.）, zymosan A （20 mg/kg, i.p., once every 4 days） or zymosan A and Rb1 （40 mg/kg, i.p., once daily）, respectively.All animals were fed a high-fat diet for 10 weeks.At scheduled time points, pathological changes in the aorta were observed using Sudan IV staining and transmission electron microscopy.White blood cell count was used to assess the inflammation.The expression of NFκB, TNFα, IL6 was evaluated by real time PCR, immunohistochemistry and ELISA, respectively.Results Typical atherosclerotic changes such as fatty streaks, plaque, foam cells in the rats following zymosan A induction were alleviated by Rb1 treatment.In the Rb1-treated group, there was a markedly decreased expression of NFκB, TNFα, and IL6.Conclusion The model of atherosclerosis can be established by inflammation based on high-fat diet in rats.Rb1 inhibits atherosclerosis through anti-inflammatory effect.