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目的研究丹参酮ⅡA磺酸钠(sodium tanshinoneⅡA sulfonate,STS)对新生猪血浆基质金属蛋白酶MMP-2和MMP-9以及重组人MMP-2和MMP-9蛋白活性的影响。方法给予新生猪STS(0.1～10 mg/kg,n=8)或生理盐水(对照组,n=4)静脉注射,每个剂量输注结束后收集动脉血,另取对照组血标本(n=6),与STS(0.1～100μg/ml)在37℃孵育30 min,均经离心后收集血浆标本储藏在-80℃。采用酶学法测定标本中MMP-2和MMP-9的活性,同时测定重组人类rhMMP-2和MMP-9与STS(0.1～1 000μg/ml)孵育后的活性。结果静脉注射STS 0.1～10 mg/kg并不影响血浆MMP-2和MMP-9的活性;动脉血体外与1～100μg/ml的STS孵育时显著增高MMP-9的活性。STS在0.1～10μg/ml浓度范围内呈剂量依赖性增加重组MMPs的活性,但在100和1 000μg/ml时显著抑制MMPs的活性。结论丹参酮ⅡA对MMP-9和MMP-2具有直接的双向调节作用,治疗剂量促进MMP-9的活性,但这种活性在健康新生个体体内受到抑制。
Objective To investigate the effects of sodium tanshinoneⅡA sulfonate (STS) on the activity of MMP-2 and MMP-9 and MMP-2 and MMP-9 in plasma of newborn pigs. Methods Neonatal pigs were intravenously injected with STS (0.1-10 mg / kg, n = 8) or normal saline (n = 4). The arterial blood was collected after the infusion of each dose. = 6) were incubated with STS (0.1 ~ 100μg / ml) at 37 ℃ for 30 min. After centrifugation, plasma samples were collected and stored at -80 ℃. The activity of MMP-2 and MMP-9 in specimens was determined by enzymatic method and the activity of recombinant human rhMMP-2 and MMP-9 after incubation with STS (0.1-1000 μg / ml) was determined. Results STS 0.1 ~ 10 mg / kg did not affect the activity of MMP-2 and MMP-9 in plasma. When incubated with STS at 1 ~ 100μg / ml, the activity of MMP-9 increased significantly. STS increased the activity of recombinant MMPs in the concentration range of 0.1 ~ 10μg / ml in a dose-dependent manner, but significantly inhibited the activity of MMPs at 100 and 1 000μg / ml. Conclusion Tanshinone Ⅱ A has a direct bidirectional regulation of MMP-9 and MMP-2, and the therapeutic dose can promote the activity of MMP-9, but this activity is inhibited in healthy newborn individuals.