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目的:探讨丹酚酸B盐(SA-B)影响纤维化心脏基膜型基质金属蛋白酶及其抑制物的抗心肌纤维化作用机制。方法:腹主动脉不完全结扎法制备大鼠心肌肥厚模型。大鼠随机分为假手术组、模型组、丹酚酸B盐低、中、高剂量组(10,20,40 mg.kg-1.d-1)和卡托普利组(40 mg.kg-1.d-1)。HE和天狼星红胶原染色法观察左心室组织病理和胶原沉积改变;Western印迹法分析心肌组织Ⅳ型胶原,MMP-2/9及TIMP-2蛋白表达;明胶酶谱法测定MMP-2/9活性。结果:SA-B干预组较模型组大鼠心肌炎性减轻,胶原沉积减少,心肌组织Hyp含量显著下降,纤维化程度明显减轻;模型大鼠心肌组织Ⅳ型胶原,MMP-2/9,TIMP-2蛋白表达以及MMP-2活性明显升高,SA-B干预组降低Ⅳ型胶原,MMP-2/9和TIMP-2蛋白表达,降低MMP-2活性,中、高剂量组作用更为明显。结论:SA-B抗心肌纤维化的作用机制之一是抑制TIMP-2的表达,降低基底膜胶原酶的表达及活性,减轻正常基底膜胶原的破坏。
Objective: To investigate the anti-myocardial fibrosis mechanism of salvianolic acid B salt (SA-B) on fibrosis heart-basement membrane matrix metalloproteinase and its inhibitors. Methods: Rat model of myocardial hypertrophy was prepared by incomplete abdominal aorta ligation. Rats were randomly divided into sham operation group, model group, low, medium and high doses of salvianolic acid B (10, 20, 40 mg.kg-1.d-1) and captopril (40 mg. kg-1.d-1). Left ventricular histopathology and collagen deposition were observed by HE staining and Sirius red collagen staining. Expression of type Ⅳ collagen, MMP-2/9 and TIMP-2 were detected by Western blotting. MMP-2/9 activity was measured by gelatin zymography . Results: Compared with the untreated group, the myocardial inflammatory response and the deposition of collagen in SA-B treatment group were decreased, the content of Hyp significantly decreased and the degree of fibrosis significantly decreased in model group. The expressions of type Ⅳ collagen, MMP-2/9 and TIMP- 2 and SA-B significantly decreased the expression of type Ⅳ collagen, MMP-2/9 and TIMP-2, and decreased the activity of MMP-2, while the effect was more obvious in medium and high dose groups. CONCLUSIONS: One of the mechanisms of anti-myocardial fibrosis in SA-B is to inhibit the expression of TIMP-2, decrease the expression and activity of collagenase in basement membrane, and reduce the destruction of normal basement membrane collagen.