DOI QR코드

DOI QR Code

The Effect of Sintongchukea-tang (Shentongzhuyu-tang) on Bone Fusion in Rib Fractured Rats

신통축어탕(身痛逐瘀湯)이 늑골골절 유발 Rat의 골유합에 미치는 영향

  • Nam, Dae-Jin (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Daejeon University) ;
  • Oh, Min-Seok (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Daejeon University)
  • 남대진 (대전대학교 한의과대학 한방재활의학교실) ;
  • 오민석 (대전대학교 한의과대학 한방재활의학교실)
  • Received : 2020.06.15
  • Accepted : 2020.07.05
  • Published : 2020.07.31

Abstract

Objectives This study was designed to evaluate the bone regeneration effects of Sintongchukea-tang (SC) on rib fractured rats. Methods Rats were randomly divided into 5 groups (normal, control, positive control, SC low [SC-L] and SC high [SC-H]). All groups were subject to fractured rib except normal group. Normal group received no treatment at all. Control group was orally fed with phosphate buffered saline, and positive control group was medicated with tramadol (20 mg/kg). SC group was orally medicated with SC (50 mg/kg, 100 mg/kg) once a day for 14 days. The fracture healing process was observed by x-ray, micro CT and fracture tissue slide was observed by immunohistochemical staining. We analysed levels of transforming growth factor-β1, Ki67, alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), receptor activator of nuclear factor kappa-β, tartrate resistant acid phosphatase (TRAP) and analysed levels of Osteocalcin in plasma. We measured levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, blood urea nitrogen (BUN) and creatinine in plasma, for hepatotoxicity and nephrotoxicity of SC. Results Though X-ray and micro-computed tomography, more callus formation was observed and bone union was progressing. Through Hematoxylin and Eosin, callus formation was increased compared to the control group. Runx2 level at SC-H was significantly increased and TRAP level at SC-L was significantly decreased compared with the control group. AST, ALT, ALP, BUN and creatinine were not statistically different from the control group. Conclusions As described above, SC promoted fracture healing by stimulating the bone regeneration factor. And SC shows no hepatotoxicity and nephrotoxicity. In conclusion, it seems that SC helps to promote fracture regeneration and it can be used clinically to patients with fracture.

Keywords

References

  1. The Korean Orthopaedic Association. Orthopaedics. 7th ed. Seoul:Choisin Medical Publishing Co. 2013:779-831, 1153-75, 1177.
  2. Hole JW. Human anatomy and physiology. Dubuque: W.C. Brown Publishers. 1993:170-227.
  3. Suh YS, Kim YB, Choi HS, Yoon HK, Seo GW, Lee BI. Postoperative mortality and the associated factors in elderly patients with hip fracture. Journal of the Korean Orthopaedic Association. 2012;47(6):445-51. https://doi.org/10.4055/jkoa.2012.47.6.445
  4. Shin KM, Jung CY, Hwang MS, Lee SD, Kim KH, Kim KS. Effects of administration of pyritum on fracture healing in mice. The Journal of Korean Acupuncture & Moxibustion Society. 2009;26(5):65-75.
  5. The Society of Korean Medicine Rehabilitation. Korean Medicine Rehabilitation. 4th ed. Paju:Koonja Publishing. 2015:206-10.
  6. Hadjiargyrou M, McLeod K, Ryaby J, Rubin C. Enhancement of fracture healing by low intensity ultrasound. Clinical Orthopaedics & Related Research. 1998;355:216-29.
  7. Goodship AE, Cunningham JL, Kenwright J. Strain rate and timing of stimulation in mechanical modulation of fracture healing. Clin Orthop Relat Res. 1998;355:105-15.
  8. Wang D. Medical secrets of an official. Seoul:Seongbo Publishers Co. 1975:749-50.
  9. Son SM. Invaluable prescriptions for emergencies. Beijing:The People' Medical Publishing House. 1982:454-5.
  10. Jo G. Seongje chongnok. Seoul:Yeo Gang Publishing Company. 1987:460-64.
  11. Wang QR, Yilingaicuo. Taibei:Tailian Guofeng Publisher. 1975:65.
  12. Lee KS, Na YH, Cha YS, Heo Y, Kim DH, Han SH. Effects of Sintongchukeo-tang on the cultured spinal sensory neurons injured by hydrogen peroxide. The Journal of Internal Korean Medicine. 2001;22(4):557-65.
  13. Kim DS. Effect of Shintongchugeotang on the intravascular coagulation induced by endotoxin in rats [dissertation]. Seongnam:Kyungwon University; 1988.
  14. Son JG. Experimental studies of the Sintonchugeotang and Sintongchugeotanggamibang on the carrageeninpretreated rats [dissertation]. Seoul:Kyunghee University; 1996.
  15. Ryu JY. Study on the anti-inflammatory, analgesic and anti-thrombotic effects of Shintongchugeotang in the experimental animals [dissertation]. Iksan:Wonkwang University; 1996.
  16. Lee KH. Study on the effects of Shentongzhuyutang on experimental blood stasis model induced by compression [dissertation]. Seoul:Kyunghee University; 1997.
  17. Lee KS. Effects of Sintongchukeotang on the cultured spinal sensory neurons injured by hydrogen peroxide [dissertation]. Iksan:Wonkwang University; 2000.
  18. Park JW. Effects of Sintongchukeatang water extract on cultured osteoblast damaged by xanthine oxidase/hypoxanthine(XO/HX) [dissertation]. Iksan:Wonkwang University; 2001.
  19. Park JW. Effects of Sintongchukeatang on the ovariectomized rat model of postmenopausal osteoporosis [dissertation]. Iksan:Wonkwang University; 2003.
  20. Kerr-Valentic MA, Arthur M, Mullins RJ, Pearson TE, Mayberry JC: Rib fracture pain and disability: can we do better? J Trauma. 2003;54:1058-63. https://doi.org/10.1097/01.TA.0000060262.76267.EF
  21. Kang JH, Lee SK, Seo MB, Na JY, Jang JH, Kim KY. A clinical study of intercostal neuropathy after rib fracture. The Korean Journal of Thoracic and Cardiovascular Surgery. 2010;43(1):53-7. https://doi.org/10.5090/kjtcs.2010.43.1.53
  22. Kim HY, Kim MY. Management of patients with rib fractures: analysis of the risk factors affecting the outcome. Korean Society for Thoracic and Cardiovascular Surgery. 2010;43(3):285-91. https://doi.org/10.5090/kjtcs.2010.43.3.285
  23. Song GY, Chi JG, Ham EK. Essential pathology. 1st ed. Seoul:Korea Medical Book Publishihng Company. 1998:772.
  24. Sung SC, Choi IH, Lee MC, Park SC, Song GY. Expression of osteocalcin and transglutaminase C during fracture healing and distraction osteogenesis in rat's tibia. J Korean Orthop Assoc. 1994;29(5):1312-25.
  25. Hulth A. Current concepts of fracture healing. Clin Orthop Relat Res. 1989;(249):265-84.
  26. Park JY. Eastern physical therapy Medicine. Seoul: Komoonsa. 1993:325.
  27. Oh G. Uijonggeumgam. Seoul:Bupin Publishing Company. 2006:1250.
  28. Jeon SC. Sanggwaboyo. Seoul:Iljung Publishing Company. 1992:176.
  29. Jung YJ. Review of clinical research about the central post-stroke pain and thalamic syndrome with Korean medicine [dissertation]. Busan:Dong-Eui University; 2018.
  30. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22(3):659-61. https://doi.org/10.1096/fj.07-9574lsf
  31. Matsumoto K, Matsunaga S, Imamura T. Expression and distribution of transforming growth $factor-{\beta}$ and decorin during fracture healing. In Vivo. 1994;8(3):215-20.
  32. Scotlandi K, Serra M, Manara MC, Maurici D, Benini S, Nini G, Campanacci M, Baldini N. Clinical relevance of Ki-67 expression in bone tumors. Orthopaedic Research Society. 1995;75(3):806-14.
  33. Kim DY. Biochemical markers of bone formation. Korean Journal of Bone Metabolism. 1994;1(1):233-9.
  34. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymphnode organogenesis. Nature. 1999;397:315-23. https://doi.org/10.1038/16852
  35. Nobta M, Tsukazaki T, Shibata Y. Critical regulation of bone morphogenetic protein-induced osteoblastic differentiation by Delta1/Jagged1-activated Notch1 signaling. The Journal of Biological Chemistry. 2005;280(16):15842-8. https://doi.org/10.1074/jbc.M412891200
  36. Komori T. Regulation of skeletal development by the Runx family of transcription factors. Journal of Cellular Biochemistry. 2005;95(3):445-53. https://doi.org/10.1002/jcb.20420
  37. Roodman GD. Advances in bone biology, the osteoclast. Endocrine Reviews. 1996;17:308-32. https://doi.org/10.1210/edrv-17-4-308
  38. Rhee SH, Park JS, Yeo HS, Choi YK, Jun CY, Park CH, Kim DW. Relationship between herb-medicine and liver damage. J Int Korean Med. 2006;27(3):572-8.
  39. Sipes IG, McQueen CA, Grandolifi AJ. Comprehensive toxicology. 3rd ed. Didcot:Pergamon. 1997:251-71.
  40. Reichling JJ, Kaplan MM. Clinical use of serum enzymes in liver disease. Dig Dis Sci. 1988;33(12):1601-14. https://doi.org/10.1007/BF01535953
  41. Kim HS. Effects of the Saururus chinensis Baill hotwater extract intake on the lipid components and metabolic enzyme activities in hyperlipidemic rats. Kor J Exercise Nutr. 2006;10:99-106.
  42. Kwon SK, Son DC, Song WS. A study of effects on renal function from continuous long-term herbal medication. The Journal of Korean Oriental Internal Medicine. 2004;25(4):300-5.
  43. Sisson JA. Handbook of clinical pathology. Philadelphia: J.B. Lippincott Co. 1976:164-205.
  44. Price PA. Role of vitamin-K-dependent proteins in bone metabolism. Annual Review of Nutrition. 1988;8:565-83. https://doi.org/10.1146/annurev.nu.08.070188.003025
  45. Price PA, Parthermore JG, Doftos LJ. New biochemical marker for bone metabolism. J Clin Invest. 1980;66(5):878-83. https://doi.org/10.1172/JCI109954