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目的观察天香丹对载脂蛋白E基因敲除[Apo E(-/-)]小鼠血清及心肌组织中基质金属蛋白酶9(MMP-9)及基质金属蛋白酶抑制剂1(TIMP-1)表达的影响,探讨天香丹稳定斑块的作用及其可能机制。方法50只8周龄Apo E(-/-)小鼠分为正常对照组(12只,给予普通饲料室温饲养),高脂饲料复合寒燥环境组(38只,给予高脂饲料和人工气候箱干预)。喂养12周后,在成功复制Apo E(-/-)小鼠动脉粥样硬化秽浊痰阻证模型的基础上,分为3组:模型组、天香丹组[2.7 g/(kg·d)]、阿托伐他汀[组6.1 mg/(kg·d)]。继续相应处理12周后,处死各组小鼠,酶联免疫双抗夹心(ELISA)法检测血清MMP-9和TIMP-1含量;实时荧光定量PCR(RT-PCR)检测心肌组织中MMP-9、TIMP-1 m RNA表达水平。结果模型组小鼠血清中MMP-9含量及心肌组织中MMP-9 m RNA表达水平较正常对照组均明显升高,差异具有统计学意义(P<0.01);与模型组比较,天香丹组小鼠血清中MMP-9含量及心肌组织中MMP-9 m RNA表达水平均明显降低,差异具有统计学意义(P<0.01),血清中TIMP-1含量及心肌组织中TIMP-1 m RNA表达水平较模型组均明显升高,差异具有统计学意义(P<0.01)。结论天香丹可能通过抑制MMP-9的表达,促进TIMP-1的表达,稳定粥样硬化斑块。
Objective To observe the expression of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in serum and myocardial tissue of apolipoprotein E gene knockout [Apo E (- / - To investigate the role of the stable plaque and the possible mechanism. Methods Fifty eight-week old Apo E (- / -) mice were divided into normal control group (n = 12, fed with common diet at room temperature), high fat diet combined with chilly environment group (fed with high fat diet and artificial climate Box intervention). On the basis of successful replication of the atherosclerotic turbid phlegm blocking model of Apo E (- / -) mice after 12 weeks of feeding, the rats were divided into 3 groups: model group, Tianxiangdan group [2.7 g / (kg · d )], Atorvastatin [group 6.1 mg / (kg · d)]. After 12 weeks, the mice in each group were sacrificed and the serum levels of MMP-9 and TIMP-1 were detected by enzyme linked immunosorbent assay (ELISA). The levels of MMP-9 , TIMP-1 m RNA expression levels. Results The level of MMP-9 in myocardium and the expression of MMP-9 mRNA in myocardial tissue in model group were significantly higher than those in normal control group (P <0.01). Compared with model group, The level of MMP-9 in myocardium and the expression of MMP-9 mRNA in myocardium were significantly decreased, the difference was statistically significant (P <0.01), the level of TIMP-1 in serum and the expression of TIMP-1 mRNA in myocardium Compared with the model group, the levels were significantly increased, the difference was statistically significant (P <0.01). Conclusion Tianxiang Dan may stabilize the atherosclerotic plaque by inhibiting the expression of MMP-9, promoting the expression of TIMP-1.