邓老冠心方对ApoE^(-/-)小鼠动脉粥样硬化不稳定斑块NOX4的影响

Effect of Denglao Guanxin Recipe on NOX4 in Unstable Plaque in ApoE Knock-out Mice with Atherosclerosis

【目的】探讨邓老冠心方防治动脉粥样硬化(AS)不稳定斑块发生发展的可能作用机制。【方法】以高脂饲料喂养雄性载脂蛋白E基因敲除(ApoE^(-/-))鼠12周,复制AS小鼠模型。将AS小鼠随机分成模型组,中药高剂量组、低剂量组,辛伐他汀组,每组10只。另设C57BL/6J小鼠10只作为正常对照组。中药高剂量组、低剂量组给予邓老冠心方(剂量分别为3 500、700mg·kg^(-1)·d^(-1))灌胃,辛伐他汀组给予辛伐他汀(剂量为0.005 mg·kg^(-1)·d^(-1))灌胃,共给药12周。采用苏木素—伊红(HE)染色法观察小鼠胸主动脉组织病理学变化,采用实时定量PCR(qPCR)法检测各组小鼠胸主动脉组织尼克酰胺腺嘌呤二核苷酸氧化酶4(NOX4)mRNA的表达。【结果】与模型组比较,中药高、低剂量组及辛伐他汀组的斑块面积/管腔面积比值呈不同程度降低(P <0.05或P <0.01)。与正常对照组比较,模型组小鼠胸主动脉组织NOX4 mRNA表达水平明显升高(P <0.001);各药物处理组小鼠胸主动脉组织NOX4 mRNA表达水平较模型组均显著降低(P <0.01),其中中药高剂量组下降最明显,与辛伐他汀组、中药低剂量组比较,差异均有统计学意义(P <0.05)。【结论】邓老冠心方可增加斑块的稳定性,并具有剂量依赖性,其机制可能与降低AS小鼠胸主动脉组织中NOX4 mRNA的表达有关。

Objective To explore the possible therapeutic mechanism of Denglao Guanxin Recipe（DGR, a experienced recipe for the treatment of coronary heart disease prescribed by DENG Tie-Tao）on the formation andrupture of unstable plaque of atherosclerosis（AS）. Methods The male ApoE knock-out（ApoE-/-）mice were fedwith high-fat diet for 13 weeks to induce AS model. And then the modeled mice were randomly divided into modelgroup, high-and low-dose Chinese medicine groups, and simvastatin group, 10 mice in each group.Additionally,10 C57 BL/6 J mice served as the normal control group. The high-and low-dose Chinese medicinegroups were given intragastric administration of DGR（at the dosage of 3 500,700 mg·kg-1·d-1 respectively）,andthe simvastatin group was given intragastric administration of 0.005 mg·kg-1·d-1 of simvastatin,the medicationcovering 12 weeks. The histopathological features of mouse thoracic aorta tissues were observed by hematoxylin andeosin（HE）staining method,and the mRNA expression of nicotinamide-adenine dinucleotide phosphate oxidase 4（NOX4）in mouse thoracic aorta of each group was detected by real-time quantitative PCR（qPCR）. Results Compared with the model group,the ratio of plaque area to lumen area was reduced to various degrees in high-and low-dose Chinese medicine groups and simvastatin group（P 〈 0.05 or P 〈 0.01）. Compared with the normalcontrol group,the mRNA expression level of NOX4 in mouse thoracic aorta of the model group was increased（P 〈0.001）. NOX4 mRNA expression level in various medication groups was decreased compared with that in the modelgroup（P 〈 0.01）, particularly in the high-dose Chinese medicine group, the difference being significant incomparison with low-dose Chinese medicine group and simvastatin group（P 〈 0.05）. Conclusion DGR has certaineffect on stabilizing the atherosclerotic plaques in dose-dependent manner. Its mechanism might be associated with the decrease of the mRNA expression level of NOX4 in mouse thoracic aorta tissues.