Wu Qi, Peng Yuan, Meng Qianchao, Cui Hongyan, Wang Xiaoning
Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Zhongguo Zhong Yao Za Zhi. 2011 Sep;36(17):2388-92.
To observe the effect of salviandic acid B (SA-B) on MMP-2/9 and TIMP-2 of fibrotic cardiac tissues in rats and explore the action mechanism of SA-B anti-fibrosis of heart.
Ventricular remodeling model was induced by abdominal aortic banding (AAB) in rats. Rats were randomly divided into 6 groups: normal, model, SA-B high, SA-B middle, SA-B low and captopril control group. Histological changes of heart were observed with hemotoxylin and eosin (H&E) staining and Sirius red staining. Hydroxyproline (Hyp) content in heart tissue was measured by hydrolysis method. Expression of heart tissue collagen NIV, MMP-2/9 and TIMP-2 were analyzed with Western blot The activities of heart tissue MMP-2 were determined with gelatin zymography substrate degradation method.
SA-B treated groups had lower heart inflammation and lower heart Hyp content; decreased Collagen deposit and alleviated cardiac fibrosis. SA-B treated groups obviously decreased the expression of Collagen IV, MMP-2/9 and TIMP-2. The activity of MMP-2 was decreased in treated SA-B treated groups.
The mechanism of SA-B action against cardiac fibrosis may be related to down-regulating the expression of TIMP -2 and the activity of MMP-2/9, thus protect the normal basal membrane.
观察丹酚酸B（SA-B）对大鼠心脏纤维化组织中基质金属蛋白酶-2/9（MMP-2/9）和金属蛋白酶组织抑制因子-2（TIMP-2）的影响，探讨SA-B抗心脏纤维化的作用机制。
采用腹主动脉缩窄（AAB）法诱导大鼠心室重构模型。将大鼠随机分为6组：正常组、模型组、SA-B高剂量组、SA-B中剂量组、SA-B低剂量组和卡托普利对照组。采用苏木精-伊红（H&E）染色和天狼星红染色观察心脏组织学变化。采用水解法测定心脏组织中羟脯氨酸（Hyp）含量。采用蛋白质免疫印迹法分析心脏组织中Ⅳ型胶原、MMP-2/9和TIMP-2的表达。采用明胶酶谱底物降解法测定心脏组织中MMP-2的活性。
SA-B治疗组心脏炎症减轻，心脏Hyp含量降低；胶原沉积减少，心脏纤维化减轻。SA-B治疗组明显降低了Ⅳ型胶原、MMP-2/9和TIMP-2的表达。SA-B治疗组MMP-2的活性降低。
SA-B抗心脏纤维化的作用机制可能与下调TIMP-2的表达及MMP-2/9的活性，从而保护正常基底膜有关。
