葛根素改善动脉粥样硬化大鼠血脂异常及炎症反应的作用机制

目的观察葛根素对动脉粥样硬化(AS)大鼠血脂代谢及血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL^-1β,以及丝裂原活化激酶(MAPK)信号通路的影响,探讨葛根素抗AS的机制。方法成年雄性Wistar大鼠60只,随机分为正常对照组(15只)与模型组(45只),模型组大鼠给予高脂饲料+腹腔注射维生素D3,复制大鼠AS模型,周期为9周。造模成功后,将模型组大鼠随机分为模型对照组、辛伐他汀组(4 mg·kg^-1·d^-1,灌胃)及葛根素大(60 mg·kg^-1·d^-1,灌胃)、小(30 mg·kg^-1·d^-1,灌胃)剂量组,每组各10只,除正常对照组与模型对照组外,其余各组大鼠均连续给药4周。检测各组大鼠血脂、血清TNF-α、IL-6、IL^-1β水平及胸主动脉组织中ERK1/2、p38、JNK及其磷酸化蛋白表达情况。结果与模型对照组比较,辛伐他汀组及葛根素大、小剂量组大鼠血清TC、TG、LDL-C、TNF-α、IL-6、IL^-1β水平均显著降低(P<0.05),血清HDL-C水平显著升高(P<0.05),胸主动脉组织p-ERK1/2、p-p38及p-JNK蛋白表达水平均显著降低(P<0.05)。结论葛根素可显著调节AS大鼠血脂水平,显著降低血清炎症因子水平,其作用机制可能与抑制MAPK信号通路激活有关。

Mechanisms of Puerarin in Improving Ameliorate Dyslipidemia and Inflammation in Atherosclerotic Rats

Objective To observe the effects of puerarin on blood lipid metabolism,serum inflammatory factors TNF-α,IL-6,IL^-1β,and mitogen-activated kinase(MAPK)signaling pathway in atherosclerotic rats,and to explore the mechanism of puerarin against atherosclersis(AS).Methods Sixty adult male Wistar rats were randomly divided into normal control group(n=15)and model group(n=45).Rats in the model group were given high-fat diet and injected with vitamin D3 to duplicate AS model.After confirming the success of the modeling,the rats in the model group were randomly divided into model control group,simvastatin group(4 mg·kg^-1·d-1,ig),high-dose puerarin(60 mg·kg^-1·d-1,ig),and low-dose puerarin(30 mg·kg^-1·d-1,ig)groups,with 10 rats in each group.Serum lipids and levels of TNF-α,IL-6 and IL^-1βin rats were measured.Results Compared with the model control group,the levels of TC,TG,LDL-C,TNF-α,IL-6,and IL^-1βin serum of rats in simvastatin group,high-dose and low-dose puerarin groups were significantly lower(P<0.05),while the levels of HDL-C in serum were significantly higher(P<0.05).The expression levels of p-ERK1/2,p-p38 and p-JNK in thoracic aorta were significantly decreased(P<0.05).Conclusion Puerarin can significantly regulate the level of serum lipids and inflammatory factors in AS rats.The mechanism may be related to the inhibition of activation of MAPK signaling pathway.