芹菜素对动脉粥样硬化大鼠氧化应激和炎性反应的影响

Effect of apigenin on oxidative stress and inflammatory response in rats with atherosclerosis

目的研究芹菜素对动脉粥样硬化大鼠氧化应激和炎性反应的影响。方法将实验用大鼠120只随机分为正常对照组、模型组、芹菜素(20、40、80 mg/kg)预处理组和辛伐他汀(1.8 mg/kg)预处理组。除正常对照组外,其余各组大鼠采用高脂饲料喂养加注射VD3的方法制备大鼠早期动脉粥样硬化模型,造模过程中芹菜素预处理组和辛伐他汀预处理组每天灌胃给药1次,而正常对照组和模型组以等量生理盐水灌胃。12周后,测定各组大鼠血清中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)的活性和丙二醛(MDA)、一氧化氮合酶(NOS)、活性氧簇(ROS)的含量以及血浆中炎症细胞因子[C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)、白介素-10(IL-10)]的水平,通过HE染色观察主动脉形态学变化并进行主动脉病变分级。结果与模型组比较,芹菜素40、80 mg/kg预处理组大鼠血清中SOD、CAT活性显著升高(P<0.05或P<0.01),MDA、NOS、ROS含量显著降低(P<0.05或P<0.01),芹菜素80 mg/kg预处理组GSH-Px活性显著升高(P<0.01);芹菜素40、80 mg/kg预处理组血浆中CRP、TNF-α、IL-1β、IL-6水平均显著降低(P<0.05或P<0.01),且芹菜素80 mg/kg预处理组IL-10水平显著升高(P<0.01)。主动脉病理性形态学变化显著改善,主动脉病变分级显著降低,以芹菜素80 mg/kg预处理组效果最为显著(P<0.01)。结论芹菜素具有抑制动脉粥样硬化大鼠氧化应激损伤和炎性反应的作用。

Objective To investigate the effects of apigenin on oxidative stress and inflammatory response in rats with atherosclerosis. Methods One hundred and twenty experimental rats were randomly divided into six groups： normal control group, model group, apigenin （20, 40, 80 mg/kg） pretreatment group and Simvastatin （1.8 mg/kg） pretreatment group. Except the rats in normal control group, the rats of the other groups were taken the method of feeding with high fat and injecting VD3 so as to make the model of rats with early atherosclerosis. During the experiment, the apigenin pretreatment group and Simvastatin pretreatment group were given drugs by intragastric administration, once a day, while the rats in the normal control group and model group were given equal volumed normal saline by intragastric ad- ministration. Twelve weeks later, the activity of superoxide dismutase （SOD）, glutathion peroxidase （GSH-Px）, catalase （CAT） and the contents of malondialdehyde （MDA）, nitric oxide synthase （NOS）, reactive oxygen species （ROS） and the levels of inflammatory cytokines [C-reactive protein （CRP）, tumour necrosis factor α（TNF-α）, interleukin 1β （IL-1β）, interleukin 6 （IL-6）, interleukin 10 （IL-10）] in serum were determined; the morphological changes of aorta was ob- served by HE staining and aortic lesions were graded. Results Compared with model group, the activity of SOD, CAT in serum of apigenin 40, 80 mg/kg pretreatment group was significantly increased （P 〈 0.05 or P 〈 0.01）, the contents of MDA, NOS, ROS in serum were significantly decreased （P 〈 0.05 or P 〈 0.01）, and the activity of GSH-Px in serum of apigenin 80 mg/kg pretreatment group was significantly increased （P 〈 0.01）; the levels of CRP, TNF-α, IL-1β , IL- 6 in plasma of apigenin 40, 80 mg/kg pretreatment group were all significantly decreased （P 〈 0.05 or P 〈 0.01）, and the level of IL-10 in apigenin 80 mg/kg pretreatment group was significantly increased （P 〈 0.01）; the histopathological changes were significantly improved, and the aortic lesions were significantly decreased, especially in apigenin 80 mg/ kg pretreatment group （P 〈 0.01）. Conclusion Apigenin has inhibiting effects on oxidative stress damage and inflamma- tory response in atherosclerosis rats.