香青兰总黄酮对ApoE^(-/-)小鼠动脉粥样硬化病变中TGF-β1/Smad信号通路及基质金属蛋白酶表达的影响

Effect of Dracocephalum moldavica total flavones on expression of TGF-β1/Smad signaling pathway and matrix metalloproteinase of atherosclerosis ApoE^(-/-) mice

研究香青兰总黄酮(TFDM)对高脂饮食诱导载脂蛋白E基因敲除(ApoE^(-/-))小鼠动脉粥样硬化形成的影响及其相关机制。采用40只SPF级8周龄雄性ApoE^(-/-)小鼠予高脂饲料喂养,随机分为5组:香青兰总黄酮低、中、高剂量组分别给予21,42,84 mg·kg^(-1)·d^(-1)灌胃;辛伐他汀组灌服辛伐他汀3.5 mg·kg^(-1)·d^(-1);模型组灌服等剂量生理盐水。另设8只相同基因背景和周龄的雄性C57BL/6J小鼠为对照组予普通饲料喂养。各组均灌胃干预12周,采用HE染色观察主动脉病理形态学变化;qRT-PCR法检测组织中TGF-β1,Smad2,Smad3,MMP-2和MMP-9基因的水平。实验结果显示:与模型组比较,HE染色观察TFDM给药组表现主动脉粥样硬化组织损伤明显减轻;TFDM不同剂量组可在一定程度上抑制高脂饲料诱导的ApoE^(-/-)小鼠主动脉TGF-β1,Smad2,Smad3,MMP-2,MMP-9 mRNA的表达,且呈现一定的剂量依赖关系趋势。提示TFDM具有减缓小鼠动脉粥样硬化形成的作用,其作用机制可能与干预TGF-β1/Smad信号转导有关。

To investigate the effect and mechanism of Dracocephalum moldovica total flavones （TFDM） on the formation of athero- sclerosis ApoE-/- mice induced by high fat diet. A total of 40 SPF 8-week-old male ApoE-/- mice were fed with high fat diet and ran- domly divided into 5 groups. TFDM high, medium, low-dose group were given 21, 42, 84 mg · kg-1· d-1 by gavage; Simvastatin group was fed with simvastatin 3.5 mg· kg- 1· d-1 ; and model group was given the same dose of mormal saline. The other eight male C57BL/6J mice of the same genetic background and age were set up as control group and fed with common diet. All of the groups were intragastrically intervened for 12 weeks. The aortic pathologic changes were observed with HE; qRT-PCR was adopted to detect TGF- β1 , Smad2, Smad3, MMP-2 and MMP-9 gene levels in tissues. Compared with model group, HE staining in TFDM group showed ob- vious relief of aortic atherosclerotic tissue injury; each TFDM group showed inhibition in mRNA expressions of TGF-β1, Smad2,Smad3, MMP-2 and MMP-9. This suggests that TFDM can inhibit atherosclerosis formation, which may be related to the intervention of TGF-β1/Smads signal transduction.