六郁同治法对动脉粥样硬化小鼠易损斑块胶原代谢的影响

Effects of Six Stagnations Elimination Therapy on Collagen Metabolism of Atherosclerotic Mice with Vulnerable Plaques

目的观察六郁同治法对动脉粥样硬化小鼠易损斑块处Ⅰ型、Ⅲ型胶原的含量及基质金属蛋白酶-9(MMP-9)表达的影响,探讨其稳定易损斑块的机制。方法采用高脂饮食喂养ApoE基因敲除小鼠的方法建立易损斑块模型。将小鼠分为正常组、模型组、中药高剂量组、中药低剂量组、辛伐他汀组,每组10只,给药组给予相应药物干预,模型组和正常组给予等量生理盐水,12周后,用苦味酸-天狼星红染色观察Ⅰ型、Ⅲ型胶原,免疫组化法检测MMP-9表达。结果与正常组比较,模型组形成易损斑块;与模型组比较,中药高、低剂量组Ⅰ型胶原增加、Ⅲ型胶原减少(P<0.01),Ⅲ型胶原/Ⅰ型胶原比值降低(P<0.01),MMP-9表达减少(P<0.01)。结论六郁同治法可稳定易损斑块,调节Ⅰ型、Ⅲ胶原的含量和抑制MMP-9的表达可能是其作用机制之一。

ObjectiveTo observe the effects of six stagnations elimination therapy on the content of typeⅠ, typeⅢ collagens and matrix metalloproteinase-9 （MMP-9） expression in atherosclerotic mice with vulnerable plaques, to discuss the possible mechanisms of this therapy in stabilizing vulnerable plaques.Methods The ApoE knockout mice were fed on high-fat diets, which built the vulnerable plaques model. Five groups were established, including normal group, model group, high-dose group, low-dose group, and simvastatin group, with 10 mice in each group. Dose groups were given drug intervention, while normal group and model group were given in the same amount of saline. After 12 weeks of drug intervention, the mice were put to death. TypeⅠ and typeⅢcollagens were observed using picric acid-Sirius red staining method. The expression of MMP-9 was detected by immunohistochemical method.ResultsCompared with normal group, vulnerable plaques formed more easily in model group.Compared with model group, typeⅠ collagen increased in high-does and low-dose groups, while typeⅢ collagen, the ratio of typeⅢ andⅠ collagens, and the expression of MMP-9 decreased （P〈0.01）.ConclusionSix stagnations elimination therapy could stabilize vulnerable plaques. Regulating typeⅠ andⅢ collagens content and inhibiting the expression of MMP-9 may be one of its possible mechanisms.