| Attention is always paid to the stability after orthodontic tooth movement and relapse of malocclusion will discount the satisfactory therapeutic efficacy at different degree. Nowadays to prevent such relapse clinically, the most commonly advocated measure is careful retention., but mechanical retainer dose harm to appearance and dental hygiene, and the retainer needs to be wore for a long time. Some adults and patients with paradentosis need to wear mechanical retainer for whole life, which brings difficulties to effects of retention and patients'cooperation. Therefore, it is important to accelerate teeth stable soon in the new position, decrease the extent of relapse after tooth movement, shorten retention time for adult and perondontitis patients clinically.In recent years, with the development of medicine, Numerous reports have described the pharmacological control of tooth movement, such as non-steroidal anti-inflammatory drugs, vitamin D3,local administration of prostaglandins, osteocalcin, PTH, bisphosphonates, local OPG gene transfer to the periodontal tissue. Although mechanisms of action of these medicine are different, they all aim at control periodontal tissue rebuilding to control tooth movement. This experiment aims to look for appropriate medicine and find out its mechanism of action as the valid assistance method of orthodontic retention period.In 1999,Mundy et al. firstly reported that statins have the effects of increasing expression of BMP-2 mRNA,promoting cytopoiesis of osteoblast and osteal anabolic metabolism by experiments in vivo and in vitro,which drew wide attention.In later researches Simvastatin has marked effect of promoting skeleton formation in union of fracture and treatment of bone defect and bone rarefaction,and Simvastatin has little adverse effect and good tolerance in long-term use,so the drug is thought highly in clinical application.Research by Wu Zhe et al. showed that local application of polymerid with Simvastatin can induce bone formation in tooth crypt after tooth extraction, conserve remaining length and bone mass of alveolar crest. Research by Han Guanghong et al. showed that simvastatin by system administration could effectly promote bone anabolic metabolism of partial alveolar bone in retention stage and the appropriate dose is 2.5mg/kg/d.BMP-2 increases bone formation by promoting differentiation of ancestral cells and osteoblasts inside cavitas medullaris to osteocytes,inducing differentiation of non-osseous tissue-origin cells to osteocytes, stimulating collagen synthesis, promoting alkaline phosphatase activity in cells and accelerating mineralized tuberculation. Endothelial cell growth factor(VEGF) is a kind of highly special mitogen of vascular endothelial cells,and its main function is to promote vascular endothelial cell proliferation, to promote angiopoiesis and maturation,and to play an important role in vascular anagenesis.It also influences bone metabolism.The purpose of the present experiment is to study the effect of simvastatin by system administration for tooth relapse length and to evaluate the effect of simvastatin on the control of tooth relapse movement;to study the changes of expression of BMP-2 and VEGF in periodontal tissue after administration of simvastatin and mechanism of action to promote periodontal tissue remodeling. Provide a dependable medicial assistance to promote moved tooth stable and shorten rentention time in clinic.Method:choose 78 male Wister rats and randomly divide them into 13groups,6rats per group. (1)blank control group:6 rats with no disposal; (2)negative control group:including 6 groups and 6 rats per group.Under the anchorage of rats'front teeth,orthodontic tooth mesial movement of upper first molar by the force for 50g,and 20d later fix retainer on left arches for respectively 1d,3d,7d,14d,21d and 28d.During retention stage normal sodium will be injected intraperitoneally for once a day. (3)experimental group: including 6 groups and 6 rats per group. Dispose same as negative control group and inject Simvastatin solution instead of normal sodium.Make plaster model of rats'upper mandible and measure tooth relapse length respectively at the end of adding force and retention.By the end of retention kill the rats by heart perfusion and get upper arch sample,make mesiodistal pathological section,HE stain and immunohistochemistry stain and study the periodontal tissue of moved tooth and the changes of BMP-2 and VEGF expression.Results:The tooth relapse distance in both non-retaining sides of negative control group and experimental group is longer than that in retaining sides(t=4.64,P<0.05;t=3.39,P<0.05). The tooth relapse distance in non-retaining side of negative control group is longer than that in non-retaining side of experimental group(t′=2.56,P<0.05).There is no difference between the tooth relapse distance in both retaining sides of negative control group and experimental group(t′=1.18,P>0.05).HE staining reveals that the recovery remodeling of periodontal tissue in experimental group is faster than that in negative control group. Positive bone resorption happens at the distal sides of moved teeth in non-retaining sides of the two groups and mainly bone formation 21 days later; positive bone resorption rarely happens in retaining sides and the periodontal tissue recovers to normal state in early stage.Time and medicine significantly influence the expression of BMP-2(F=17.24,P<0.05;F=118.81,P<0.05).The BMP-2 expression decreases in 7th day in in non-retaining sides of negative control group,gradually increases later and decreases again in 28th day; The BMP-2 expression decreases in 7th day in non-retaining sides of experimental group and gradually increases later. The BMP-2 expression gradually decreases in retaining sides of negative control group; The BMP-2 expression gradually increases in retaining sides of experimental group.BMP-2 expresses more in both retaining and non-retaining sides of experimental group than that does in negative control group(F=2155.74,P<0.05;F=117.41,P<0.05).In retaining sides of 28th-day group in negative control group and blank control group,there is no difference in gray value of BMP-2 expression(q′=1.60, P>0.05) and gray value of blank control group is less than that of the other groups(P<0.01).Time and medicine significantly influence the expression of VEGF(F=16.31,P<0.05;F=109.36,P<0.05). The VEGF expression increases in 7th day in non-retaining sides of both negative control group and experimental group, decreases in 14th day and increases again later gradually;no obvious change in VEGF expression happens in the prophase of retaining sides of negative control group and the expression decreases in later period; VEGF expression gradually increases in retaining sides of experimental group but no obvious change happens in the later period of retention. VEGF expresses more in both retaining and non-retaining sides of experimental group than that does in negative control group(F=1957.68,P<0.05;F=411.59,P<0.05). .In retaining sides of 28th-day group in negative control group and blank control group,there is no difference in VEGF expression(q=2.413,P>0.05) and VEGF expression of blank control group is less than that of the other groups(P<0.01).Conclusion: The study indicates that 1. systemic administration of simvastatin can inhibit the relapse extent after rat orthodontic movement and it can assist to get tooth stability in retention stage as together with mechanical retainer simvastatin can well prevent relapse tooth movement. 2. simvastatin by system administration accelerates the recovery of periodontal tissue after orthodontic movement.3. simvastatin can increase the expression of BMP-2 and VEGF in periodontal tissue so that it can promote osteocyte formation ,bone mineralization, angiopoiesis and maturation, That might be the mechanism of action for simvastatin to accelerate the periodontal tissue remodeling. |
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