黄连提取物对动脉硬化小鼠斑块胶原类型及MMP-9/TIMP-1 比值 的影响*

目的:探讨黄连提取物对高脂喂养ApoE-/-小鼠主动脉AS斑块内胶原类型及基质金属蛋白酶-9( MMP-9)与基质金属蛋白酶组织抑制剂( TIMP-1)比值的影响,探讨黄连提取物稳定斑块的可能作用机制.方法:33只6-8周龄的ApoE基因敲除小鼠予高脂喂养13周后,待其形成成熟的AS斑块后,随机分为3组:模型组、黄连提取物组、辛伐他汀组(阳性对照组),每组11只.继续高脂喂养,并按体重比折算给予小鼠临床推荐剂量的相应药物治疗13周,处死动物,每只小鼠取主动脉根部的4个切面,行天狼猩红染色,检测各组小鼠主动脉斑块内Ⅰ、Ⅲ型胶原含量,以及斑块内MMP-9和TIMP-1的表达,计算MMP-9/TIMP-1比值.结果:给药13周后,图像分析结果显示,黄连提取物组小鼠主动脉斑块内Ⅰ型胶原含量与模型组比较有所增加,但无显著差异(P＞0.05)；辛伐他汀组和黄连提取物组小鼠主动脉斑块内Ⅲ型胶原含量与模型组比较显著降低(P＜0.01).Ⅲ型/Ⅰ型胶原比值,两给药组与模型组比较均显著降低(P＜0.01).与模型组比较,黄连提取物和辛伐他汀组小鼠主动脉斑块内MMP-9的阳性表达均明显减少(P＜0.01),黄连提取物组主动脉斑块内TIMP-1的阳性表达与模型组相比明显增加(P＜0.01),辛伐他汀组TIMP-1表达有所增加,但无统计学差异(P＞0.05),两给药组之间比较无显著差异(P＞0.05).各给药组中MMP-9/TIMP-1比值均有所降低,与模型组比较具有显著差异(P＜0.05,P＜0.01).结论:在临床推荐剂量下,黄连提取物可明显改善ApoE-/-小鼠主动脉AS斑块内胶原类型,调整斑块内MMP-9/TIMP-1比值,从而促进斑块稳定.

Effect of Coptis Root Extract on Collagen category and the Ratio of MMP-9 to TIMP-1 in Aortic Vulnerable Atherosclerotic plaque of ApoE-gene Knockout Mice*

Objective: To observe the effect of Coptis Root Extract(CRE) on collagen category and the ratio of MMP-9 to TIMP-1 in aortic vulnerable atherosclerotic plaque of high fat fed ApoE-gene knockout mice for exploring the possible mechanism to stabilize vulnerable plaque.Methods: Thirty-three ApoE-gene knockout mice,6-8 week age,were fed with high-fat diet for 13 weeks.After mature atherosclerotic plaque being formed,the animals were randomly allocated into three groups: the control group,the CRE group,the sim-vastatin group(as positive control),11 in each group.They were continuously fed with high-fat diet and the two drug-treated groups,respective drugs in clinically recommended dose were given for another 13 weeks.Then all mice were sacrificed by the end of experi-ment.4 sections of aortic roots in each mouse were examined by Sirius red staining.The contents of typeⅠand Ⅲ collagen and the expressions of MMP-9 and TIMP-1 in atherosclerotic plaque were detected and their ratios were caculated.Results: After treatment for 13 weeks,compared with that of the control group,the expression of typeⅠcollagen in aortic atherosclerotic plaque in CRE group was increased but not significant(P > 0.05),while the expressions of type Ⅲ collagen and the ratio of type Ⅲ to typeⅠcollagen in aortic atherosclerotic plaque in CRE group and simvastatin group were significantly reduced(P<0.01).Compared with that of the control group,the positive expressions of MMP-9 in plaque on CRE group and simvastatin group were significantly reduced(P<0.01),the ex-pression of TIMP-1 in plaque on CRE group was significantly increased(P<0.01).The expression of TIMP-1 in plaque on simvastatin group was increased but not significantly(P > 0.05).The difference between the two drug treatment group was not significant(P > 0.05).The ratios of MMP-9 to TIMP-1 on the two drug treatment groups were significantly reduced compared with those of the control group(P<0.05,P<0.01).Conclusions: In a clinically recommended dose,CRT can significantly modify the collagen category and the ratio of MMP-9 to TIMP-1 in atherosclerotic plaque of ApoE-gene knockout mice to do favor to plaque stability.