Zhang Hui, Song Yu, Li Zhiyong, Zhang Ting, Zeng Li
Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xingxiang, China.
Department of Cerebral Surgery of The Third People's Hospital of Anyang City, Anyang, China.
Am J Surg. 2016 Jun;211(6):1143-52. doi: 10.1016/j.amjsurg.2015.05.037. Epub 2015 Aug 29.
Adhesion formation, which results from mechanical peritoneal damage, tissue ischemia, or the presence of foreign materials, is a complicated process. The formation of adhesions is associated with inflammatory response and extracellular matrix deposition in response to injury. Although the pathophysiology of adhesion formation is widely understood, an absolute solution to this problem does not exist yet. As a main component of Erigeron breviscapus, breviscapine has exhibited the ability of anti-inflammatory and antifibrosis on many diseases. The purpose of this study was to investigate the effect of breviscapine on the development of postoperative intra-abdominal adhesions in Wistar rats.
Abdominal adhesions were induced by scraping the cecum in rats. Various dosages of breviscapine drugs were administered for 10 days after surgery. On the 11th day after surgery, the levels of interleukin (IL) 18, IL-6, tumor necrosis factor α in blood serum and transforming growth factor β1 (TGF-β1), connective tissue growth factor, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) in peritoneal fluid were determined by enzyme linked immunosorbent assay. The expression of Smad7 and TGF-β1 in rat cecum tissue was evaluated by Western blot analysis. Grades of intestinal adhesion were ranked by macroscopic observation.
The intraperitoneal administration of breviscapine is effective on the prevention of the formation of postoperative adhesions in rats. Breviscapine decreased the levels of IL-18, IL-6, and tumor necrosis factor-α in blood serum and TGF-β1, connective tissue growth factor, PAI-1 in peritoneal fluid. But the levels of tPA and the ratio of tPA and PAI-1 in peritoneal fluid were increased. In addition, breviscapine significantly inhibited the expression of TGF-β1 and increased the level of Smad7 in the rat cecum tissue.
These results suggested that intraperitoneal administration of breviscapine was effective in preventing intra-abdominal adhesion formation in rats. Breviscapine appears to have synergetic effects which could decrease fibrosis by inhibiting inflammation, upregulating peritoneal fibrinolytic activity and regulating the TGF and/or Smad signaling pathway. These data indicated a potential new therapeutic use of breviscapine on adhesion prevention.
粘连形成是一个复杂的过程,它由机械性腹膜损伤、组织缺血或异物存在引起。粘连的形成与损伤后的炎症反应和细胞外基质沉积有关。尽管粘连形成的病理生理学已被广泛了解,但尚未找到解决这一问题的绝对方法。灯盏花素作为灯盏细辛的主要成分,已在多种疾病中表现出抗炎和抗纤维化的能力。本研究的目的是探讨灯盏花素对Wistar大鼠术后腹腔粘连形成的影响。
通过刮擦大鼠盲肠诱导腹部粘连。术后给予不同剂量的灯盏花素药物,持续10天。术后第11天,采用酶联免疫吸附测定法测定血清中白细胞介素(IL)-18、IL-6、肿瘤坏死因子α水平以及腹腔液中转化生长因子β1(TGF-β1)、结缔组织生长因子、组织型纤溶酶原激活剂(tPA)、纤溶酶原激活剂抑制剂1(PAI-1)水平。通过蛋白质印迹分析评估大鼠盲肠组织中Smad7和TGF-β1的表达。通过宏观观察对肠粘连程度进行分级。
腹腔注射灯盏花素对预防大鼠术后粘连形成有效。灯盏花素降低了血清中IL-18、IL-6和肿瘤坏死因子-α水平以及腹腔液中TGF-β1、结缔组织生长因子、PAI-1水平。但腹腔液中tPA水平以及tPA与PAI-1的比值升高。此外,灯盏花素显著抑制大鼠盲肠组织中TGF-β1的表达并提高Smad7水平。
这些结果表明腹腔注射灯盏花素可有效预防大鼠腹腔粘连形成。灯盏花素似乎具有协同作用,可通过抑制炎症、上调腹腔纤维蛋白溶解活性以及调节TGF和/或Smad信号通路来减少纤维化。这些数据表明灯盏花素在预防粘连方面具有潜在的新治疗用途。