【摘要】：目的本研究通過建立大鼠Ⅰ型糖尿病下頜骨骨折模型，觀察辛伐他汀與胰島素聯(lián)合用藥對糖尿病大鼠下頜骨骨折愈合過程中骨痂形態(tài)、骨密度的影響，聯(lián)合檢測血清中堿性磷酸酶及骨鈣素濃度、骨痂中骨鈣素的表達情況，以探討辛伐他汀對糖尿病下頜骨骨折是否有促進愈合作用，，為糖尿病病人選擇促進骨愈合藥物提供理論依據(jù)。 方法選用6～8周齡，體重300±20gWistar大鼠96只，按隨機原則分為4組，對照組（A組），糖尿病骨折組（B組），糖尿病骨折+胰島素組（C組），糖尿病骨折+胰島素+辛伐他汀組（D組），每組24只。適應性喂養(yǎng)2w后，開始Ⅰ型糖尿病動物模型的建立。分別給予糖尿病骨折組、糖尿病骨折+胰島素組、糖尿病骨折+胰島素+辛伐他汀組大鼠一次性大劑量腹腔注射鏈脲佐菌素（STZ）50mg/kg。三天后，測定三組大鼠的血糖濃度，血糖濃度≥16.7mmol/L視作造模成功�；謴惋曫B(yǎng)3d后，開始四組大鼠的下頜骨骨折模型建立。全麻下用打磨機金剛砂片在大鼠下頜骨體下緣咬肌嵴的遠中末端處制作1mm寬、3mm長的貫穿頰舌側(cè)的不完全骨缺損。術(shù)后，糖尿病骨折+胰島素組及糖尿病骨折+胰島素+辛伐他汀組給予胰島素控制血糖。辛伐他汀配成懸濁液，給予糖尿病骨折+胰島素+辛伐他汀組每天10mg/kg灌胃，余下各組予以等量生理鹽水灌胃。分別于術(shù)后2w，4w，6w，8w每組各處死大鼠6只，抽取血清樣本，使用ELISA試劑盒測得血清中ALP及BGP的濃度。取大鼠的下頜骨標本行骨密度和X線片檢查，然后置于4％多聚甲醛中固定48h，再使用10％乙二胺四乙酸進行為期60d的組織脫鈣。脫鈣完成后，組織塊石蠟包埋行HE染色組織形態(tài)學觀察及BGP免疫組織化學檢測。 結(jié)果1除A組外，余下三組大鼠在注射鏈脲佐菌素72h后，測得血糖濃度均高于16.7mmol/L，并逐漸出現(xiàn)典型的糖尿病“三多一少”癥狀。骨折模型建立后，慶大霉素肌注1w，周圍軟組織傷口無紅腫，無感染。2成模后于2w，4w，6w，8w在各組間進行X線比較：2w時各組間X線片顯示大鼠骨折線密度均較低，4w，6w，8w時D組均較B組骨折線密度增高，骨折線模糊。骨密度比較：術(shù)后4w，6w，8w時D組測得骨密度高于B組（P＜0.05），有統(tǒng)計學意義。4w時，D組較A組骨密度低（P＜0.05），有統(tǒng)計學意義。8w時，D組較C組骨密度高（P＜0.05），有統(tǒng)計學意義。血清骨鈣素濃度比較：2w、4w、6w、8w時，D組大鼠血清骨鈣素濃度均高于B組（P＜0.05），有統(tǒng)計學意義。2w、4w時，D組血清骨鈣素濃度高于C組（P＜0.05），有統(tǒng)計學意義。血清堿性磷酸酶濃度比較：2w，4w，6w，8w時，D組血清堿性磷酸酶濃度均高于B組（P＜0.05），有統(tǒng)計學意義。2w、4w時，D組高于C組（P＜0.05），有統(tǒng)計學意義。組織形態(tài)學觀察：D組在2w，4w，6w，8w里骨小梁數(shù)量、骨小梁寬度、骨小梁長度等均優(yōu)于B組。免疫組化檢測：2w，4w，6w時，D組骨痂區(qū)骨鈣素的表達均高于B組、C組（P＜0.05），有統(tǒng)計學意義。 結(jié)論1通過一次性大劑量注射STZ的方法可以快速誘導建立糖尿病大鼠模型及通過大鼠下頜骨體制作1mm×3mm貫穿大鼠頰舌側(cè)的骨缺損，可以建立下頜骨不完全性骨折實驗動物模型。2動物實驗證實糖尿病各組骨折愈合情況較對照組差，糖尿病可導致骨愈合延遲。3辛伐他汀可提高糖尿病大鼠骨折區(qū)BGP和ALP的表達，辛伐他汀與胰島素聯(lián)合用藥可促進Ⅰ型糖尿病大鼠下頜骨骨折的愈合。
[Abstract]:Objective To investigate the effects of simvastatin combined with insulin on callus morphology and bone mineral density during mandibular fracture healing in diabetic rats by establishing a model of type I diabetic mandibular fracture in rats. Whether Ting can promote the healing of diabetic mandibular fracture provides a theoretical basis for diabetic patients to choose drugs to promote bone healing.
Methods Ninety-six Wistar rats aged 6-8 weeks and weighing 300+20 g were randomly divided into 4 groups: control group (group A), diabetic fracture group (group B), diabetic fracture + insulin group (group C), diabetic fracture + insulin + simvastatin group (group D), 24 rats in each group. After 2 weeks of adaptive feeding, the animal model of type I diabetes mellitus was established. After three days of intraperitoneal injection of streptozotocin (STZ) 50 mg/kg, the blood glucose concentrations of the three groups were determined. The concentration of blood glucose (> 16.7 mmol/L) was regarded as a successful model. The mandibular fracture models of the four groups were established after 3 days of recovery. The distal end of the masseter ridge at the lower margin of the mandible of rats was made with grinding machine diamond tablets under general anesthesia to produce incomplete bone defect with a width of 1 mm and a length of 3 mm through the cheek and tongue. After operation, the diabetic fracture + insulin group and the diabetic fracture + insulin + Simvastatin group were given insulin to control blood sugar. Six rats in each group were sacrificed at 2w, 4w, 6W and 8W after operation. Serum samples were taken and the concentrations of ALP and BGP in serum were measured by ELISA kit. Bone mineral density (BMD) and X-ray films were taken from the mandibular bone specimens of the rats and placed in 4% of the rats. Polyformaldehyde was immobilized for 48 hours and then decalcified with 10% ethylenediaminetetraacetic acid for 60 days.
Results 1 Except group A, the blood glucose concentration of the other three groups was higher than 16.7 mmol/L 72 hours after injection of streptozotocin, and the typical symptoms of diabetes mellitus gradually appeared. After the establishment of the fracture model, gentamicin was injected intramuscularly for 1 week, and the wounds around the soft tissue were not inflamed and inflamed. The bone mineral density of group D was higher than that of group B at 4w, 6W and 8W after operation (P < 0.05). The bone mineral density of group D was higher than that of group B at 4w, 6W and 8W after operation (P < 0.05). The bone mineral density of group D was lower than that of group A at 4W (P < 0.05). The serum levels of osteocalcin in group D were higher than those in group B at 2w, 4w, 6W and 8W (P < 0.05). The serum levels of osteocalcin in group D were higher than those in group C at 2w, 4w, 6W and 8W (P < 0.05). The concentration of phosphatase in group D was higher than that in group B (P Group P (0.05) was statistically significant.
Conclusion 1 The diabetic rat model can be established by injecting STZ in a large dose at once and the 1 mm 65 Urinary disease can lead to delayed bone healing. 3 Simvastatin can increase the expression of BGP and ALP in the fracture area of diabetic rats. Simvastatin combined with insulin can promote the healing of mandibular fracture in type I diabetic rats.
【學位授予單位】：河北聯(lián)合大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R587.1;R782.4

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