| BackgroundIn spinal surgery,degenerative lumbar intervertebral disc disease is a com mon and frequent disease.And when intervertebral disc degeneration happened, there are different levels of structure degenerative change including involving intervertebral discs, cartilage endplate, joint ashdod and the yellow ligaments. Previous research in this area were more concentrated in the nucleus pulposus and annulus of the above, but only little research of angiogenesis in degener ative lumbar disc disease be researched. With further research,angiogenesis in d egenerative lumbar disc disease has played an important role in unanimous ap proval.However, the role of angiogenesis, there are two different argument:one believes that angiogenesis can improve blood supply and nutrition which is a disease of the lesion repair.Another argument is that the physiological state of the disc is no blood supply organization, and vascular invasion may meet th e matrix metalloproteinases matrix-degrading enzymes such as the conditions r equired for activation, leading to matrix degradation, disc degeneration occurs.I n the past, the study found, COX-2in ischemic tissue hypoxia upregulated, a nd its increase can affect the way through their formation of new blood vesse Is. In this study, first established the rat lumbar degeneration model.And then study the affect of different types of cyclooxygenase-2(COX-2) inhibitors on the rat model of disc degeneration which can provide a reference to disc deg eneration disease.With the population aging,degenerative disease of the spine surgery has b ecome common,and lumbar disc degeneration degenerative spine disease is the most multipleand common type.Clinicalmore performance for nerve root or s pinal cord compression caused by back pain after lower limb radiation pain, r educed muscle strength, paresthesia and muscle atrophy.The results showed tha t the degeneration of spinal disc degeneration occurred in the first part.Althou gh the date of this degenerative disc disease of the mechanisms remains uncle ar, but with the recent development of molecular biology,the study of its mec hanism is no longer confined to traditional mechanical factors,but from the po int of view and the immune meristem point of view of the causes of disc de generation line arguments, degeneration of intervertebral disc is the premise an d basis pathological process of a series of lumbar degenerative disease such a s disc herniation, degenerative spondylolisthesis, spinal stenosis and segmental instability.When the pathological changes above occur,spine,nerve root and cau da equian will be compressed,and lead to meropresthesia, muscle weakness an d sphincter disturbances. Cervicodynia,lumbodynia or radiating ache in under body will occur if nerve root is compressed and become inflamed,or stimulat ion of sinuvertebral nerve ending. At present, it has clearly that process of in tervertebral disc degeneration mean water and proteoglycan is reducing, type I collagen is increasing within the nucleus pulposus,it lead to reduction of loadi ng capacity of intervertebral disc,The exact mechanism attracted lumbar inter vertebral disc degeneration is still inconclusive. The occurrence of lumbar disc degeneration in addition to the traditional mechanical factors, neuro-psycholog ical factors and biochemical factors, but also closely related to immune respon se. The cytokines and inflammatory mediators had played an increasingly imp ortant role in intervertebral disc degeneration. The important role of neovascula rization in intervertebral disc degeneration process is inconclusive. Some schol ars abroad believed that the angiogenesis was the body trying to repair tissue damage and the spontaneous reaction to delaying the process,because passive diffusion of nutrients from endplate and anulus fibrosus decrease. However,ot hers believed that the disc vascularization caused disc degeneration occurs bec ause matrix-degrading zymogens get activity from blood,and it was the pathol ogical basis of disc degeneration, so it was harmful to the body. There are n ew blood vessel formation and disc tray and lower proteoglycan content of n ucleus pulposus cells to apoptosis and other research theories.Cyclooxygenase-2(COX-2) factor is a multifunctional protein, there are at least two isomerase of cyclooxygenase in mammals:COX-1and COX-2.CO X-2is a inducible protein, and it is highly expressed in many malignant tissu es, which closely related to tumor angiogenesis,beside,COX-2is a rate-limiting enzyme to catalysts arachidonic acid into prostaglandins material. COX-2has Various ways to regulate tumor angiogenesis process,such as up-regulation of VEGF and bel-2. Metabolite of arachidonic acid such as TXA2and PGE2,w hich can induce angiogenesis, moreover,COX-2can inhibits endothelial cells a poptosis. The study found that selectively COX-2inhibitors has significant i nhibition of gastric cancer angiogenesis. There are no vessel in normal intervert ebral disc,but it is very common in degenerative disc. Some studies have sho wn that factor COX-2expression was significantly higher in degenerative inter vertebral disc tissue than in normal disc. Hypoxia-inducible factor-1(HIF-la) is an oxygen-dependent transcriptional activator and can trigger the transcription of downstream genes through a hyp oxia response element (HRE) binding. HIF-la is an important molecule for ce lls to adapt to the hypoxia. Diffusion of nutrients decrease lead to insufficient supply of nutrients and relatively hypoxic environment in degenerative interv ertebral disc.some scholars have confirmed that the expression of HIF-la wa s significantly higher than the normal disc by the method of the immunohisto chemistry. When the tumor grows rapidly, it will definitely lead to serious loc al tissue hypoxia and induce the expression of HIF-1α. HIF-1α is thought be involved in new blood vessel formation in tumors by the following ways:(1) Start-up stage,it up-regulate VEGF and it’s ligand result in increased permeabi lity of the vessel.(2) Progressing stage,it up-regulate MMPs,and promote VEG F to induce vascular endothelial cell proliferation and migration,with the help of angiopoietin, form a new vessels sprout.(3)Forming stage,with the help of VEGF, angiopoietin and integrin,a single vessels sprout form vascular lumen, and anastomosis into vascular network with some small blood vessels near.(4) Modeling stage, with the help of plate let derived grow the factor, angiopoi etin, form a intact vascular wall.Studies have shown that COX-2, HIF-1a in tumor angiogenesis are the i mportant factor,andHIF-lahas been proven even more expression in human int ervertebral discs. The expressed within the organization and with degenerative disc the formation of new blood vessels within the relationship between the d egeneration of the intervertebral disc to reveal the formation mechanism of ne w blood vessels, and the treatment of disc degeneration are of great significan ce. ObjectiveCOX-2and HIF-la is highly expressed in many malignant tumor tissues, and they are closelyrelated to the neovascularization.Some scholars thought ne ovascularization in intervertebral disc is an important factor of degeneration. T he expression of COX-2and HIF-1α have even been confirmed in the human intervertebral disc.Explore the affect of different types of cyclooxygenase-2(COX-2) inhibitors on the rat model of disc degeneration which can provide a reference to disc degeneration disease.MethodsSelect60cases of the12-month-old SPF SD rats and first established th e animal model of lumbar disc degeneration. All ratsrespectively use6.5%chl oral hydrate anesthetized by intraperitoneal injection,prone position, the fixed1imbs, lower back skin preparation, sterile draping, along the lower back spine to do after the incision, cut skin along the subperio steal dissection rongeur t o remove the center of the waist to L1-Slspinous process, articular process, s upraspinous, interspinous ligament, cutting off bilateral vertical spine muscles, and then by layer closure of subcutaneous fascia the skin. Placed in a separat e cage in captivity. Simple random divided into4groups of15for one grou p:The control group use placebo10mg·kg’-1·d-1to gavage;Celecoxib group use use celecoxib capsules10mg· kg-1·d-1to gavage; Nimesulide group use ni mesulide particles10mg· kg-1·d-1to gavage and The two-drug group use eel ecoxib capsules5mg·kg-1·d-1and nimesulide particles5mg·kg-1·d-1.All fed a tot al of8weeks. Detected the expression of hypoxia-inducible factor-la (HIF-la)、vascular endo thelial growth factor (VEGF) and the level of proteoglycan of intervertebral di sc tissue.calculated the chondrocyte apoptosis index (AI). Results1.The HIF-la and VEGF of the Control group was negative, and the other gr oups were Masculine.All expressed in the cytoplasm, nucleus stained yellow.T he mixed drug group was more effective.Compared the positive expression of HIF-la and VEGF,the differences were statistically significant(P<0.05).2.Placebo group fed only the nucleus pulposus cells with high expression of HIF-la, COX-2inhibitors.when use COX-2inhibitors after the intervention, t he expression of HIF-la was decrease. The combination effect was obvious. At the same time,explorethe expression of VEGF protein. The protein expressi on of VEGF inthecontrol group was significantin crease.whenuse COX-2inhi bitorsto intervene, VEGF expression was decreased. The combination group was more obvious too.3.The proteoglycan levels of the control group was (1.31±0.02) pg/mg, and os teoblast apoptosis index (AI) was (43.81±2.88); Nimesulide group was (2.06±0.06) pg/mg、(27.67±2.08); Celecoxib celecoxib group was (2.19±0.10) pg/mg、(28.67±0.58); Compared with the two-drug group (2.62±0.10) pg/mg、(23.67±1.53).Visible,the proteoglycan levels of the medication group were significantly i ncreased,but osteoblast apoptosis index (AI) were decreased.What’s more,the m ixed drug group was more effective and the differences were statistically signi ficant (P<0.05).4.Test the proteoglycan content of the different groups of disc degeneration m odel.You can saw that thecontrol group was the most serious loss of proteogl yean.when feed different concentrations of COX-2inhibitors, proteoglycan los s relative to mitigate and the drug combination was more obvious;In addition, by TUNEL staining of tissue,you can found the apoptosis phenomenon in the control group was most significant.When use COX-2inhibitors,the apoptotic phenomenon relative to mitigate and the drug combination was more obvious too.Conclusion1.The reason called degeneration is that constitute intervertebral disc tissue co mponents appear biochemical reactions under the influence of various factors.T hese organizations ingredients to make changes in the nature, number, and mo rphology, eventually leading to dysfunction loss. In the disc degeneration occu rs, you can see a lack of oxygen and the phenomenon of the new blood ves.2. Neovascularization plays an important role in disc degeneration.while a larg e number of studies show that COX-2factor and angiogenesis is also closely related. When use the inhibition of COX-2,all of the disc degeneration has a good therapeutic effect.COX-2, the main factors involved in disc degeneratio n by stimulating the intervertebral disc capillary proliferation.3.The results of this study confirmed that the use of COX-2inhibitors on CO X-2inhibition can effectively alleviate the symptoms of disc degeneration, sig nificant clinical effect.When use mixed COX-2inhibitors to suppress, the treat ment effect is more obvious.It has a certain synergy between each inhibitor.4.Thestudy found, the proteoglycan loss as well as apoptosis are the most seri ous of the groups did not useCOX-2inhibitors.when feeding different concentr ations of COX-2inhibitors, proteoglycan loss and apoptosis were lessened.So we can speculate that In disc degeneration,apoptosis and proteoglycan loss ma y be an important mechanism. |
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