摘要
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 effect of sodium Tanshinone ⅡA sulfonate（STS）on the plasma matrix metalloproteinase（MMP）-2 and MMP-9 of healthy newborn piglets.Methods Healthy newborn piglets was given either STS（0.1,1 and 10 mg/kg,n = 8）or saline（n = 4）,intravenously and accumulated.A whole blood sample was collected before infusing each dose or at the end of the experiment.The sample was centrifuged and the plasma was collected for measurements of MMP-2 and-9 activities using Gelatin Zymography.Meanwhile,whole blood samples harvested from control animals were incubated with different concentrations of STS for 30 minutes and the MMP-2 and-9 activities were examined as well.To further delineate the direct effect of STS on MMPs,rhMMP-2 and-9 were incubated with STS and the activities were measured by zymography.Results Although incubation with 1-100 μg/ml of STS elevated plasma MMP-2 and MMP-9 in vitro,infusion of 0.1-10 mg/kg of STS did not affect the plasma MMP-2 and MMP-9 in vivo.Chemically,STS concentration-dependently increased rhMMP-2 and rhMMP-9 activities directly,whereas 100 and 1000 μg/ml of STS significantly inhibited the activities of these MMPs.Conclusions STS regulates the activities of MMP-9 in a bi-phase manner.STS elevates the activities of MMP-9 pharmacologically,but these effects are inhibited in vivo in healthy newborn piglets.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2011年第11期1071-1075,共5页
Journal of Clinical Pediatrics
关键词
新生猪
丹参酮ⅡA
基质金属蛋白酶
newborn piglet
Tanshinone ⅡA
matrix metalloproteinase
