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Planta Med 2014; 80(12): 969-973
DOI: 10.1055/s-0034-1382877
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Prevention of Experimental Postoperative Peritoneal Adhesions through the Intraperitoneal Administration of Tanshinone IIA

Chengxi Wang
1   Department of Pharmacology, Guangdong Pharmaceutical University, Guangzhou, China
2   Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, Guangzhou, China
,
Xiao Li
2   Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, Guangzhou, China
,
Xiao Meng
2   Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, Guangzhou, China
,
Jing Zhou
3   Department of Pharmacology, Inner Mongolia Medical University, Hohhot, China
,
Fei Qin
2   Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, Guangzhou, China
,
Lianbing Hou
2   Department of Pharmaceutical Science, Nanfang Hospital, Southern Medical University, Guangzhou, China
› Author Affiliations
Further Information

Publication History

received 08 May 2014
revised 09 June 2014

accepted 16 June 2014

Publication Date:
04 August 2014 (online)

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Abstract

Postoperative adhesions develop after nearly every abdominal surgery. The formation of adhesions is associated with the inflammatory response, fibrinolytic system, and extracellular matrix deposition in response to injury. Tanshinone IIA is one of the major extracts obtained from Salvia miltiorrhiza, which has anti-inflammatory effects on many diseases. Postoperative adhesions were induced by injuring the parietal peritoneum and cecum in Wistar rats, followed by the administration of various dosages of tanshinone IIA. The adhesion scores for each group were collected seven days after the initial laparotomy. The activity of the tissue-type plasminogen activator in the peritoneal lavage fluid was measured. The messenger ribonucleic acid expression levels of the tissue-type plasminogen activator, plasminogen activator inhibitor-1, and cyclooxygenase-2 in the ischaemic tissues were measured by quantitative real-time polymerase chain reaction. The intraperitoneal administration of tanshinone IIA is effective for the prevention of the formation of postoperative adhesions in rats. Tanshinone IIA increased fibrinolytic activity in the peritoneal lavage fluid and tissue-type plasminogen activator messenger ribonucleic acid expression in ischaemic peritoneal tissues but decreased the plasminogen activator inhibitor and cyclooxygenase-2 messenger ribonucleic acid expression significantly. These results revealed that tanshinone IIA was a potent postoperative adhesion preventer by enhancing fibrinolytic activity and decreasing cyclooxygenase-2 activity.

Key words

tanshinone IIA - peritoneal adhesions - tPA - PAI-1 - inflammatory response - peritoneal fibrinolysis - COX-2
 

  • References

  • 1 Holmdahl L, Risberg B. Adhesions prevention and complications in general surgery. Eur J Surg 1997; 163: 169-174
    PubMedSearch in Google Scholar
  • 2 Menzies D, Ellis H. Intestinal obstruction from adhesions–how big is the problem. Ann R Coll Surg Engl 1990; 72: 60-63
    PubMedSearch in Google Scholar
  • 3 Thompson J. Pathogenesis and prevention of adhesion formation. Dig Surg 1998; 15: 153-157
    CrossrefPubMedSearch in Google Scholar
  • 4 Holmdahl L. The role of fibrinolysis in adhesion formation. Eur J Surg Suppl 1997; 577: 24-31
    PubMedSearch in Google Scholar
  • 5 Lu HR, Wu Z, Pauwels P, Lijnen HR, Collen D. Comparative thrombolytic properties of tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (u-PA) and K1K2Pu (a t-PA/u-PA chimera) in a combined arterial and venous thrombosis model in the dog. J Am Coll Cardiol 1992; 19: 1350-1359
    CrossrefPubMedSearch in Google Scholar
  • 6 Runge MS, Quertermous T, Haber E. Plasminogen activators. The old and the new. Circulation 1989; 79: 217-224
    CrossrefPubMedSearch in Google Scholar
  • 7 Akyildiz H, Akcan A, Sozuer E, Kucuk C, Yilmaz N, Deniz K. The preventive effect of Met-RANTES on postoperative intraperitoneal adhesion formation in the rat model. Surgery 2008; 144: 404-409
    CrossrefPubMedSearch in Google Scholar
  • 8 Hickey MJ. Role of inducible nitric oxide synthesis in the regulation of leukocyte recruitment. Clin Sci 2001; 100: 1-12
    CrossrefPubMedSearch in Google Scholar
  • 9 Ward BC, Panitch A. Abdominal adhesions: current and novel therapies. J Surg Res 2011; 165: 91-111
    CrossrefPubMedSearch in Google Scholar
  • 10 Han JY, Fan JY, Horie Y, Miura S, Cui DH, Ishii H, Hibi T, Tsuneki H, Kimura I. Ameliorating effects of compounds derived from Salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion. Pharmacol Ther 2008; 117: 280-295
    CrossrefPubMedSearch in Google Scholar
  • 11 Yin X, Yin Y, Cao FL, Chen YF, Peng Y, Hou WG, Sun SK, Luo ZJ. Tanshinone IIA attenuates the inflammatory response and apoptosis after traumatic injury of the spinal cord in adult rats. PLoS One 2012; 7: e38381
    CrossrefPubMedSearch in Google Scholar
  • 12 Ren ZH, Tong YH, Xu W, Ma J, Chen Y. Tanshinone II A attenuates inflammatory responses of rats with myocardial infarction by reducing MCP-1 expression. Phytomedicine 2010; 17: 212-218
    CrossrefPubMedSearch in Google Scholar
  • 13 Fu J, Huang H, Liu J, Pi R, Chen J, Liu P. Tanshinone IIA protects cardiac myocytes against oxidative stress-triggered damage and apoptosis. Eur J Pharmacol 2007; 568: 213-221
    CrossrefPubMedSearch in Google Scholar
  • 14 Dong X, Dong J, Zhang R, Fan L, Liu L, Wu G. Anti-inflammatory effects of tanshinone IIA on radiation-induced microglia BV-2 cells inflammatory response. Cancer Biother Radiopharm 2009; 24: 681-687
    CrossrefPubMedSearch in Google Scholar
  • 15 Xiao M, Chenxi W, Hongfu C, Lianbing H. Effects of tanshinone IIA on fibroblast proliferation and related gene expression in rats with postoperative abdominal adhesion. Chin Tradit Herb Drugs 2012; 43: 1381-1384
    PubMedSearch in Google Scholar
  • 16 Holmdahl L, Eriksson E, Eriksson BI, Risberg B. Depression of peritoneal fibrinolysis during operation is a local response to trauma. Surgery 1998; 123: 539-544
    CrossrefPubMedSearch in Google Scholar
  • 17 Aarons CB, Cohen PA, Gower A, Reed KL, Leeman SE, Stucchi AF, Becker JM. Statins (HMG-CoA reductase inhibitors) decrease postoperative adhesions by increasing peritoneal fibrinolytic activity. Ann Surg 2007; 245: 176-184
    CrossrefPubMedSearch in Google Scholar
  • 18 Cetin M, Ak D, Duran B, Cetin A, Guvenal T, Yanar O. Use of methylene blue and N,O-carboxymethylchitosan to prevent postoperative adhesions in a rat uterine horn model. Fertil Steril 2003; 80: 698-701
    CrossrefPubMedSearch in Google Scholar
  • 19 Baykal A, Ozdemir A, Renda N, Korkmaz A, Sayek I. The effect of octreotide on postoperative adhesion formation. Can J Surg 2000; 43: 43-47
    PubMedSearch in Google Scholar
  • 20 de Boer JP, Abbink JJ, Brouwer MC, Meijer C, Roem D, Voorn GP, Lambers JW, van Mourik JA, Hack CE. PAI-1 synthesis in the human hepatoma cell line HepG2 is increased by cytokines–evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 1991; 65: 181-185
    PubMedSearch in Google Scholar
  • 21 Kruithof EK, Tran-Thang C, Ransijn A, Bachmann F. Demonstration of a fast acting inhibitor of plasminogen activators in human plasma. Blood 1984; 64: 907-913
    PubMedSearch in Google Scholar
  • 22 van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator (antiactivator) synthesised by endothelial cells. J Biol Chem 1984; 259: 14914-14921
    PubMedSearch in Google Scholar
  • 23 Segura T, Schmokel H, Hubbell JA. RNA interference targeting hypoxia inducible factor 1alpha reduces post-operative adhesions in rats. J Surg Res 2007; 141: 162-170
    CrossrefPubMedSearch in Google Scholar
  • 24 Muzii L, Marana R, Brunetti L, Margutti F, Vacca M, Mancuso S. Postoperative adhesion prevention with low-dose aspirin: effect through the selective inhibition of thromboxane production. Hum Reprod 1998; 13: 1486-1489
    CrossrefPubMedSearch in Google Scholar
  • 25 Lasson B, Svanberg SG, Swolin K. Oxyphenbutazone–an adjuvant to be used in prevention of adhesion in operations for fertility. Fertil Steril 1977; 28: 807-808
    PubMedSearch in Google Scholar
  • 26 Saed GM, Munkarah AR, Diamond MP. Cyclooxygenase-2 is expressed in human fibroblasts isolated from intraperitoneal adhesions but not from normal peritoneal tissues. Fertil Steril 2003; 79: 1404-1408
    CrossrefPubMedSearch in Google Scholar
  • 27 Greene AK, Alwayn IP, Nose V, Flynn E, Sampson D, Zurakowski D, Folkman J, Puder M. Prevention of intraabdominal adhesions using the antiangiogenic COX-2 inhibitor celecoxib. Ann Surg 2005; 242: 140-146
    CrossrefPubMedSearch in Google Scholar
  • 28 Guvenal T, Cetin A, Ozdemir H, Yanar O, Kaya T. Prevention of postoperative adhesion formation in rat uterine horn model by nimesulide: a selective COX-2 inhibitor. Hum Reprod 2001; 16: 1732-1735
    CrossrefPubMedSearch in Google Scholar
  • 29 Katada J, Saito H, Ohashi A. Significance of cyclooxygenase-2 induced via p 38 mitogen-activated protein kinase in mechanical stimulus-induced peritoneal adhesion in mice. J Pharmacol Exp Ther 2005; 313: 286-292
    PubMedSearch in Google Scholar
  • 30 Kwak HB, Sun HM, Ha H, Kim HN, Lee JH, Kim HH, Shin HI, Lee ZH. Tanshinone IIA suppresses inflammatory bone loss by inhibiting the synthesis of prostaglandin E2 in osteoblasts. Eur J Pharmacol 2008; 601: 30-37
    CrossrefPubMedSearch in Google Scholar
  • 31 Lu Y, Liu X, Liang X, Xiang L, Zhang W. Metabolomic strategy to study therapeutic and synergistic effects of tanshinone IIA, salvianolic acid B and ginsenoside Rb1 in myocardial ischemia rats. J Ethnopharmacol 2011; 134: 45-49
    CrossrefPubMedSearch in Google Scholar
  • 32 Wang L, Zhang X, Liu L, Cui L, Yang R, Li M, Du W. Tanshinone II A down-regulates HMGB1, RAGE, TLR4, NF-kappaB expression, ameliorates BBB permeability and endothelial cell function, and protects rat brains against focal ischemia. Brain Res 2009; 1321: 143-151
    PubMedSearch in Google Scholar
  • 33 Reed KL, Fruin AB, Gower AC, Stucchi AF, Leeman SE, Becker JM. A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity. Proc Natl Acad Sci 2004; 101: 9115-9120
    CrossrefPubMedSearch in Google Scholar
  • 34 Corona R, Verguts J, Schonman S, Binda MM, Mailova K, Koninckx PR. Postoperative inflammation in the abdominal cavity increases adhesion formation in a laparoscopic mouse model. Fertil Steril 2011; 95: 1224-1228
    CrossrefPubMedSearch in Google Scholar
  • 35 Tanaka Y, Fujiwara T, Hayashi T, Ezumi R. Effect of dexamethasone on the formation of intestinal adhesions following postoperative radiotherapy. Strahlentherapie 1975; 149: 608-620
    PubMedSearch in Google Scholar
  • 36 OʼBrien WF, Drake TS, Bibro MC. The use of ibuprofen and dexamethasone in the prevention of postoperative adhesion formation. Obstet Gynecol 1982; 60: 373-378
    PubMedSearch in Google Scholar
  • 37 Replogle RL, Johnson R, Gross RE. Prevention of postoperative intestinal adhesions with combined promethazine and dexamethasone therapy: experimental and clinical studies. Ann Surg 1996; 163: 580-588
    PubMedSearch in Google Scholar
  • 38 Ito T, Fraser IP, Yeo Y, Highley CB, Bellas E, Kohane DS. Anti-inflammatory function of an in situ cross-linkable conjugate hydrogel of hyaluronic acid and dexamethasone. Biomaterials 2007; 28: 1778-1786
    CrossrefPubMedSearch in Google Scholar
  • 39 Peyman S, Ashrafzadeh TM, Amirali J, Amir S. Effects of dexamethasone, piroxicam and sterile aloe vera extract on the prevention of postoperative peritoneal adhesion formation in rat. Adv Environ Biol 2012; 6: 2851-2859
    PubMedSearch in Google Scholar
  • 40 Cohen PA, Aarons CB, Gower AC, Stucchi AF, Leeman SE, Becker JM, Reed KL. The effectiveness of a single intraperitoneal infusion of a neurokinin-1 receptor antagonist in reducing postoperative adhesion formation is time dependent. Surgery 2007; 141: 368-375
    CrossrefPubMedSearch in Google Scholar
  • 41 Nair SK, Bhat IK, Aurora AL. Role of poteolytic enzyme in the prevention of the postoperative intraperitoneal adhesions. Arch Surg 1974; 108: 849-853
    CrossrefPubMedSearch in Google Scholar
  • 42 Lim R, Morrill JM, Prushik SG, Reed KL, Gower AC, Leeman SE, Stucchi AF, Becker JM. An FDA approved neurokinin-1 receptor antagonist is effective in reducing intraabdominal adhesions when administered intraperitoneally, but not orally. J Gastrointest Surg 2008; 12: 1754-1761
    CrossrefPubMedSearch in Google Scholar