麝香保心丸防治动脉粥样硬化的实验研究

Experimental Study of Shexiang Baoxin Pill in Preventing and Treating Atherosclerosis

目的研究慢性炎症反应与动脉粥样硬化的关系及麝香保心丸防治动脉粥样硬化的作用机制。方法新西兰雄性大耳白兔60只,随机分为5组,即空白对照组,模型组,麝香保心丸低、高剂量组,立普妥组。高脂饲料造模4周后再连续给药6周,末次给药后(空腹大于12 h)耳动脉采血,麻醉后取主动脉,检测血脂及炎症因子,观察各组动物动脉内膜病理形态的改变,检测Ca2+/钙调蛋白依赖性蛋白激酶II(CaMKⅡ)蛋白表达及Ca MKII的活性。结果与模型组比较,麝香保心丸低、高剂量组及立普妥组的总胆固醇(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)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞介素8(IL-8)水平及动脉粥样斑块数量、厚度均有明显降低,Ca MKII蛋白含量及活性均有明显下降,差异均有统计学意义(P<0.05,P<0.01)。结论麝香保心丸具有抗实验性新西兰大耳兔动脉粥样硬化的作用,并可能与降低CaMKⅡ蛋白含量或活性,减轻或抑制慢性炎症反应有关。

Objective To investigate the relationship of chronic inflammatory reaction with atherosclerosis（AS） and to evaluate the preventive and therapeutic effect of Shexiang Baoxin Pill（SBP） for AS. Methods A total of 60 New Zealand rabbits were randomly divided into five groups, namely normal control group, AS model group （Vehicle group）, Lipitor group, and low- and high-dose SBP groups. Except for the normal control group, the rabbits in the other four groups were fed with high fat forage for 4 weeks, and then were given the corresponding medicine for 6 continuous weeks. At the end of the last medication and after fasting over 12 hours, blood was sampled from the arteria auricularis of the rabbits for the detection of blood lipid and inflammatory factor levels. The aorta was sampled for the observation of pathological changes in the aortic intima. Moreover, Ca2＋/calmodulin-dependent protein kinase（CaMKII） protein expression and its activities were also detected. Results Compared with those in AS model group, SBP and Lipitor had obvious effects on decreasing the levels of total cholesterol（TC ）, triglyceride（TG）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, alanine aminotransferase （ALT）, aspartate aminotransferase （ AST ）, total bilirubin （ TBIL ）, direct bilirubin （DBIL）, tumor necrosis factor alpha （TNF-α ）, interleukin 6 （IL-6）, interleukin 8 （IL-8） as well as the atheromatous plaque area. Meanwhile, the content and activities of CaMKII in SBP groups and Lipitor group were decreased significantly（P 〈 0.05, P 〈 0.01 compared with the model group）. Conclusion ABP has an effect on counteracting AS in New Zealand rabbits, and the mechanism may be related to the decrease of CaMKII protein content and activities, and with the reduction of chronic inflammatoryreaction.