| Objective: acid-suppressing drugs (ASD) has become the mostimportant drug in the treatment of reflux esophagitis and stomach ulcers,which have been widely used clinically. Proton pump inhibitors (PPIs) andhistamine-2receptor antagonists (H2RAs) are the two types of the mostwidely used acid-suppressing drugs. PPIs shows a crucial role in the treatmentof gastroesophageal reflux disease, especially in the treatment of high gastricacid secretion and the prevention of NSAID gastropathy, PPI drugs aresignificantly superior to H2RAs drugs in the long-term use. However, the PPIsare not the choice drug for all of gastrointestinal diseases and PPIs are oftenused excessively. With the wide application of acid-suppressing drugs,complications absorbed more and more attention. Some researches showedthat acid-suppressing drugs, especially the PPIs, which correlated with hipfractures obviously, can increase the risk of fractures. Other studies showedthat PPI drugs had an antagonistic action on the vacuolar proton pump in theosteoclasts. The selective proton pump inhibitor in the osteoclasts was able toantagonize the osteoclast bone resorption and destroy the osteoclast activity,while the PPI drugs may increase the activity of osteoblasts, interfere with thebalance between absorption and rebuilding of the bone tissue and destroy thebone microstructure; PPI drugs also caused changes in the endocrineregulation, therefore, affected normal bone growth and metabolism. Based onthe above studies, PPI drugs may affect the process of fracture healing.Bonemorphogenetic protein (BMP) and vascular endothelial growth factor (VEGF)play an important role in the process of fracture healing.In this study, anattempt has been made to observe the influence of the expression of BMP andVEGF in the callus after taking the PPI drugs, explore the mechanism of theeffect of this drugs on the fracture healing, the result may be helpful for patients with reasonable application of the acid-suppressing drugs, reduce theincidence of fracture delayed union and non-union.Method:30clean level healthy male SD rats, body weight200±20g,were randomly divided into two groups:(1) the experimental group, preparethe model of tibial shaft fracture, daily intraperitoneal injection oflansoprazole (100mg/(Kg, d);(2) the control group, prepare the model oftibial shaft fracture, daily intraperitoneal injection same volume normal saline.In the experiment,10%chloral hydrate was used to anesthesia, byintraperitoneal injection of0.3ml/kg dose. After the success of the anesthesia,in the midline incision on the left knee, in the middle of the tibial stem,transverse fractures was made by thread saw, with a Kirschner wire (diameteris1.5mm) placing in the tibial anterogradely.after reset, we needle aKirschner wire anterogradely into the distal tibial medullary cavity, then washthe wound with saline, suture gradually. After-surgery3days, dailyintraperitoneal injection of50,000U penicillin was to prevent infection. Theadministration begin on the day of surgery, according to the weight to adjustdosage. In the experimental group,we injected into the abdominal cavity withsora (100mg/kg/d), and in the control group, with the same volume saline.During the whole experiment process, all the rats can take water and foodfreely. In each group,15rats was randomly put to death at4th week aftersurgery. The whole left intact tibia was taken out. Compare the callus size inthe two groups by the X-ray. We took the callus tissue, then put them into10%formalin fixative, which can be used to conventional fixation, embedding,sectioning and prepara bone tissue slices with the thickness about5um. Themorphological genetic changes of bone tissue was observed by HE staining. Ineach group, the dynamic change of the expression of VEGF and BMP wereobserved by the immunohistochemical staining. The results were analyzedusing the image analysis system IPP(Image-Pro Plus) for semi-quantitativeanalysis.The statistical analysis software SPSS13.0was used to analysis allthe data, which were expressed as mean±standard deviation. If the data meetthe normal distribution, comparison between the two groups with two independent samples t-test, P <0.05for statistically significant; If the data donot meet normal distribution, two independent samples nonparametric test forthe two groups,P <0.05as statistically significant.Results: In the control group, the rats tibial stem fracture callus is morethan the other group, with the fiber around the callus. The fracture linesblurred, and the Kirschner wire used to internal fixation was not loose anddisplaced without malunion and angulation; And in the experimental group,the fracture callus is less, and some fracture line is clear. Even some fracturewas not healed, and some Kirschner wires were loose and deciduous. Throughthe Goldberg scoring system, there was statistically significant differencebetween the callus of the two groups; By HE staining, in the control group, theweaving callus in the end of the rats fravture increased, only with a smallamount of cartilage callus and fibrous tissue. The bone trabecular’s thicknesswas uniform, and the lamellar bone appearanced; In the experimental group,the cartilage callus and fibrous tissue was more, but the weaving callus wasless; BMP and vascular endothelial growth factor mainly expressed on activeosteoblasts. With immunohistochemical staining, under the light microscope,cells contained obvious brownish-yellow granules, that was considered as thepositive expression.The evpression of BMP and VEGF in the bone tissue inthe control group is significantly higher than the experimental group (P <0.05).Conclusion: In the bone tissue, PPI drugs can inhibit and the expressionof VEGF and BMP,therefore, they can inhibit the formation of callus. In bonetissue morphology, fibrous tissue and cartilage callus were be found toincrease, woven bone tissue was less. PPI drugs may delayed the fracturehealing. |
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