连翘苷对创伤性骨折大鼠模型骨愈合作用的研究
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摘要
目的本研究旨在探索连翘苷(forsythin)对大鼠软组织损伤和骨愈合作用的影响。方法利用闭合式股骨干骨折术模拟大鼠创伤性骨折模型,模拟创伤性骨关节炎。SD大鼠随机分为4组:健康对照组、健康加药组、骨折模型组和模型加药组。番红O快绿染色检测大鼠骨组织变化并检测大鼠血清Ca、P含量和碱性磷酸酶(ALP)、骨钙素(BGP)活性;Western blot检测血清骨形态发生蛋白(BMP-2)、胶原和增殖标记蛋白表达水平;ELISA检测炎症因子iNOS, TNF-α和IL-6水平。结果连翘苷减轻骨折后骨组织病理损伤;与模型组相比,连翘苷增加骨折后血清Ca、P含量、ALP和BGP活性、血清BMP-2、胶原和增殖标记蛋白表达水平,减少骨折后血清炎症因子iNOS, TNF-α和IL-6水平。结论连翘苷可调节成骨指标和炎症因子,从而改善骨折软组织损伤,促进骨愈合。
The purpose of this study was to explore the effect of forsythin on soft tissue injury and bone healing in rats. A closed femoral shaft fracture was used to construct a traumatic fracture model of rats. SD rats were randomly divided into four groups: healthy control group, healthy forsythin treated group, fracture model group, and model forsythin treated group. The serum Ca, P content and alkaline phosphatase(ALP) and osteocalcin(BGP)activity were detected with commercial kit. Western blot was used to detect bone morphogenetic protein(BMP-2),collagen and proliferation marker protein expression level; ELISA was used to detect levels of inflammatory factors iNOS, TNF-α and IL-6. Data showed that forsythin reduced the histological lesion of the bone tissue after fracture.Compared with model group, the serum Ca, P content, activity of ALP and the BGP as well as the relative expression levels of BMP-2, collagen proliferation marker protein were increased by forsythin, while the serum levels of inflammatory factors iNOS, TNF-α and IL-6 were reduced. Collectively, this study showed that forsythin could regulate osteogenic index and inflammatory factors to alleviate fracture soft tissue injury and promote bone healing.
The purpose of this study was to explore the effect of forsythin on soft tissue injury and bone healing in rats. A closed femoral shaft fracture was used to construct a traumatic fracture model of rats. SD rats were randomly divided into four groups: healthy control group, healthy forsythin treated group, fracture model group, and model forsythin treated group. The serum Ca, P content and alkaline phosphatase(ALP) and osteocalcin(BGP)activity were detected with commercial kit. Western blot was used to detect bone morphogenetic protein(BMP-2),collagen and proliferation marker protein expression level; ELISA was used to detect levels of inflammatory factors iNOS, TNF-α and IL-6. Data showed that forsythin reduced the histological lesion of the bone tissue after fracture.Compared with model group, the serum Ca, P content, activity of ALP and the BGP as well as the relative expression levels of BMP-2, collagen proliferation marker protein were increased by forsythin, while the serum levels of inflammatory factors iNOS, TNF-α and IL-6 were reduced. Collectively, this study showed that forsythin could regulate osteogenic index and inflammatory factors to alleviate fracture soft tissue injury and promote bone healing.
引文
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[2]Li C,Dai Y,Zhang SX,et al.Quinoid glycosides from forsythia suspensa[J].Phytochemistry,2014,104:105-113.
[3]Zhong WT,Wu YC,Xie XX,et al.Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of mapk and nf-kappab activation in acute lung injury mice[J].Fitoterapia,2013,90:132-139.
[4]Lawyer TJ,Jankowski J,Russell GV,et al.Prevalence of post-traumatic osteoarthritis in morbidly obese patients after acetabular fracture fixation[J].J Long Term Eff Med Implants,2014,24(2/3):225-231.
[5]Akkaya S,Nazali M,Kilic A,et al.Cefazolin-sodium has no adverse effect on fracture healing in an experimental rabbit model[J].Eklem Hastalik Cerrahisi,2012,23(1):44-48.
[6]Hankenson KD,Zimmerman G,Marcucio R.Biological perspectives of delayed fracture healing[J].Injury,2014,45(Suppl 2):S8-S15.
[7]Halici M,Oner M,Guney A,et al.Melatonin promotes fracture healing in the rat model[J].Eklem Hastalik Cerrahisi,2010,21(3):172-177.
[8]Claes L,Ignatius A,Lechner R,et al.The effect of both a thoracic trauma and a soft-tissue trauma on fracture healing in a rat model[J].Acta Orthop,2011,82(2):223-227.
[9]Cui Z,Crane J,Xie H,et al.Halofuginone attenuates osteoarthritis by inhibition of tgf-beta activity and h-type vessel formation in subchondral bone[J].Ann Rheum Dis,2016,75(9):1714-1721.
[10]Pan X,Cao X,Li N,et al.Forsythin inhibits lipopolysaccharide-induced inflammation by suppressing jak-stat and p38 mapk signalings and ros production[J].Inflamm Res,2014,63(7):597-608.
[11]Song YE,Tan H,Liu KJ,et al.Effect of fluoride exposure on bone metabolism indicators alp,balp,and bgp[J].Environ Health Prev Med,2011,16(3):158-163.
[12]Kim JW,Choi KH,Yun JH,et al.Bone formation of block and particulated biphasic calcium phosphate lyophilized with escherichia coli-derived recombinant human bone morphogenetic protein 2 in rat calvarial defects[J].Oral Surg Oral Med Oral Pathol Oral Radiol Endod,2011,112(3):298-306.
[13]高舒妤,朱国宴,郭国宁.可溶性B7-H3在人脑创伤合并骨折愈合中的表达及意义[J].免疫学杂志,2018,34(1):54-58.
[14]Hosseininia S,Lindberg LR,Dahlberg LE.Cartilage collagen damage in hip osteoarthritis similar to that seen in knee osteoarthritis;a case-control study of relationship between collagen,glycosaminoglycan and cartilage swelling[J].BMC Musculoskel Dis,2013,14:18.
[15]Yetkin E,Waltenberger J.Molecular and cellular mechanisms of aortic stenosis[J].Int J Cardiol,2009,135(1):4-13.
[16]Wu J,Ding Y,Bi Y,et al.Staphylococcus aureus induces tgf-beta1 and bfgf expression through the activation of ap-1 and nf-kappab transcription factors in bovine mammary gland fibroblasts[J].Microb Pathog,2016,95:7-14.
[17]Kapoor M,Martel-Pelletier J,Lajeunesse D,et al.Role of proinflammatory cytokines in the pathophysiology of osteoarthritis[J].Nat Rev Rheumatol,2011,7(1):33-42.
[18]Wojdasiewicz P,Poniatowski LA,Szukiewicz D.The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis[J].Mediators Inflamm,2014,2014:561459.
[19]Ma Z,Wang Y,Piao T,et al.Echinocystic acid inhibits il-1beta-induced cox-2 and inos expression in human osteoarthritis chondrocytes[J].Inflammation,2016,39(2):543-549.
[20]Miller RE,Miller RJ,Malfait AM.Osteoarthritis joint pain:The cytokine connection[J].Cytokine,2014,70(2):185-193.