丹参酮ⅡA磺酸钠通过增强腹膜纤溶系统活性降低大鼠术后腹膜粘连发生  

Sodium tanshinone IIA sulfonate prevents postoperative peritoneal adhesions in rats by enhancing the activity of the peritoneal fibrinolytic system

作　　者：林思[1] 秦飞[1] 宋路瑶[1] 侯楚祺 侯连兵[1] 

机构地区：[1]南方医科大学南方医院药学部,广东广州510515 [2]南方医科大学药学院,广东广州510515

出　　处：《南方医科大学学报》2016年第2期260-264,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(30873271;81570473);广东省新药创制重大科技专项(2012A080204020)~~

摘　　要：目的评价丹参酮IIA磺酸钠(STS)对实验性大鼠术后腹膜粘连的防治作用并探讨其发生机制。方法构建大鼠术后腹膜粘连模型。75只大鼠随机分为模型组、STS高剂量组、中剂量组、低剂量组和空白组,每组15只;STS高、中、低组给药剂量分别为20、10、5 mg/kg STS,模型对照组给予等体积生理盐水,腹腔注射给药,连续7 d。各组大鼠7 d后处死,粘连分级评价,ELISA检测组织中t PA/PAI-1的水平,发色底物法检测腹腔液中t PA活性,IHC半定量检测腹膜组织中TGF-β1和Collgen-I的表达;伤口愈合强度实验考察STS是否影响伤口愈合。结果与模型组相比,STS高、中、低剂量组均降低腹膜粘连的发生;腹腔液中t PA活性显著提高,组织中t PA/PAI-1蛋白水平显著上升,TGF-β1和Collgen-I蛋白表达量显著降低。同时腹腔注射STS不会影响伤口愈合。结论腹腔注射STS可有效防治术后粘连的发生,其作用机制可能通过降低TGF-β1表达,下调其对TGF-β/Smads通路激活,降低下游PAI-1水平,从而上调腹膜纤溶系统活性实现的。Objective To evaluate the effect of sodium tanshinone IIA sulfonate（STS） in preventing postoperative peritoneal adhesions in rats and explore the mechanisms. Methods Sixty SD rats were randomized into 4 equal groups, including a blank control group, adhesion model group, and high-, moderate-, and low-dose STS-treated groups, and were subjected to injuries of the parietal peritoneum and cecum to induce peritoneal adhesions, followed by intraperitoneal administration of saline and STS at the doses of 20, 10, and 5 mg/kg for 7 consecutive days, respectively. Another 15 untreated rats served as the blank control group. The adhesion scores in each group were recorded after the treatments; the activity of tissue-type plasminogen activator（t PA） in peritoneal lavage fluid was measured, t PA/PAI- 1 protein ratio in the peritoneal tissue was determined by ELISA, and the expressions of TGF-β1 and collagen I were detected by immunohistochemistry. The anastomotic healing model was used to assess the impact of STS on wound healing. Results Intraperitoneal administration of STS effectively prevented peritoneal adhesion without affecting anastomotic healing in the rats. Compared with the adhesion model group, the STStreated groups showed increased peritoneal lavage fluid t PA activity and t PA/PAI-1 ratio in the ischemic tissues with lowered TGF- β1 and collagen I expressions in the ischemic tissues. Conclusion Intraperitoneal administration of STS can prevent peritoneal adhesion and enhance local fibrinolysis in rats, and these effects may be mediated by TGF-β signaling pathway.

关 键 词：丹参酮IIA磺酸钠 术后腹膜粘连 tPA活性 tPA/PAI-1 

分 类 号：R656.4[医药卫生—外科学]