【摘要】：第1章褪黑素水平與脊柱側(cè)凸的發(fā)病機制相關(guān)研究第1節(jié)不同劑量褪黑素對C57BL/6J雙足直立小鼠模型脊柱側(cè)凸發(fā)生率的影響目的：內(nèi)源性褪黑素(melatonin, MT)缺乏被認為是青少年特發(fā)性脊柱側(cè)凸(Adolescent idiopathic scoliosis, AIS)最重要的發(fā)病機制之一。既往研究報道低褪黑素C57BL/6J雙足直立鼠脊柱側(cè)凸的發(fā)生率較高,同時對該動物模型早期持續(xù)外源性腹腔注射生理劑量的褪黑素可阻止脊柱側(cè)凸的發(fā)生和發(fā)展。但是目前尚無研究證實該效應(yīng)是否與所注射褪黑素的劑量相關(guān)。因此,本研究旨在探究早期外源性補充不同劑量褪黑素是否會影響C57BL/6J雙足直立小鼠脊柱側(cè)凸的發(fā)生率。方法：選取三周齡C57BL/6J雌性SPF級小鼠105只,隨機選取75只施行雙上肢及鼠尾切除術(shù)建立雙足直立小鼠模型,然后行直立體態(tài)的誘導(dǎo)。將四足鼠隨機分為兩組：組A：15只,每日腹腔注射0.1ml 10%酒精/生理鹽水；組B：15只,每日注射0.1ml褪黑素溶液,劑量為8mg/kg。雙足鼠隨機分為5組：組C：15只,每日腹腔注射0.1ml 10%酒精/生理鹽水；組D、E、F、G:每組15只,每日注射O.1ml褪黑素溶液,劑量分別為4mg/k、8 mg/kg、16mg/kg、32 mg/kg。 20周后麻醉下對所有小鼠行全脊柱X線正位片檢查,測量Cobb角,Cobb角10。定義為脊柱側(cè)凸。記錄并比較各組脊柱側(cè)凸的發(fā)生率。結(jié)果：20周后,全脊柱X線正位片顯示雙足鼠中共有19只(19/75,25.3%)發(fā)生脊柱側(cè)凸,其中未注射褪黑素的C組有14只(14/15,93.3%)小鼠發(fā)生脊柱側(cè)凸,注射生理量褪黑素的E組有3只(3/15,20%)發(fā)生了脊柱側(cè)凸,D、F組各有1只(1/15,6.7%)發(fā)生脊柱側(cè)凸。四足鼠中僅A組有2只(2/15,13.3%)發(fā)生了脊柱側(cè)凸。C組小鼠的脊柱側(cè)凸發(fā)生率顯著高于其余各組。然而注射不同劑量褪黑素的D、E、F、G組間小鼠脊柱側(cè)凸的發(fā)生率無顯著差異(P0.05)。結(jié)論：褪黑素缺乏在C57BL/6J雙足直立小鼠脊柱側(cè)凸的發(fā)生發(fā)展中起著重要的作用,早期腹腔注射褪黑素可顯著降低該模型脊柱側(cè)凸的發(fā)生率,且這種效應(yīng)不依賴于褪黑素的劑量。第2章脊柱側(cè)凸的臨床治療相關(guān)研究第1節(jié) 鎖骨胸廓交角差對Lenke 1型青少年特發(fā)性脊柱側(cè)凸患者后路矯形術(shù)后雙肩平衡的預(yù)測作用目的：探討鎖骨胸廓交角差(Clavicle chest cage angle difference, CCAD)是否可用于Lenke 1型青少年特發(fā)性脊柱側(cè)凸(adolescent idiopathic scoliosis, AIS)患者后路矯形術(shù)后雙肩影像學(xué)、美學(xué)平衡及患者和術(shù)者滿意度的預(yù)測。方法：回顧性分析2008年3月至2011年8月在我院行選擇性后路矯形內(nèi)固定術(shù)、有完整影像學(xué)資料的Lenke 1型女性青少年特發(fā)性脊柱側(cè)凸患者44例,平均年齡15.1±1.7歲。CCAD為站立位全脊柱正位片上左側(cè)鎖骨胸廓的夾角(CC A)與右側(cè)CCA的差值。雙肩高度差(SHD)為站立位全脊柱正位片上左側(cè)肩鎖關(guān)節(jié)正上方軟組織影與相應(yīng)右側(cè)軟組織影高度的差值。分別測量患者術(shù)前、術(shù)后及兩年后隨訪時的CCAD及雙肩高度差SHD。末次隨訪雙肩高度差SHD≥1cm的患者歸入雙肩失衡組；SHD1cm為雙肩平衡組。在患者末次隨訪時的背部外觀照上測量其內(nèi)肩高度差(inner shoulder height, SHi)及外肩高度差(outer shoulder height, SHo)。末次隨訪SHi1cm、SHo1cm分別定義為內(nèi)肩、外肩平衡,SHi≥1cm SHo≥1cm分別定義為內(nèi)肩、外肩失衡。通過兩個問卷分別評估患者的滿意度及術(shù)者的滿意度。利用ROC曲線分析預(yù)測末次隨訪患者雙肩平衡狀態(tài)及患者和術(shù)者的滿意度的術(shù)前CCAD診斷值。結(jié)果：末次隨訪時共18例患者雙肩失衡,26例雙肩平衡。雙肩失衡組術(shù)前CCAD顯著高于雙肩平衡組(8.1±3.9。vs.3.3±1.8。,P0.001)。根據(jù)患者美學(xué)外觀照,末次隨訪內(nèi)肩平衡組和內(nèi)肩失衡組的術(shù)前CCAD無統(tǒng)計學(xué)差異,外肩平衡組和外肩失衡組術(shù)前CCAD亦無顯著差異。根據(jù)患者和術(shù)者的滿意度,不滿意組的患者術(shù)前CCAD顯著高于滿意組。ROC曲線分析術(shù)前CCAD預(yù)測術(shù)后雙肩影像學(xué)失衡、患者不滿意及術(shù)者不滿意的診斷值均為5.5。。結(jié)論：CCAD可用于預(yù)測Lenke 1型青少年特發(fā)性脊柱側(cè)凸患者術(shù)后雙肩影像學(xué)平衡及患者和術(shù)者的滿意度,但是由于雙肩美學(xué)參數(shù)和影像學(xué)參數(shù)存在不一致,CCAD不能用于預(yù)測Lenke1型青少年特發(fā)性脊柱側(cè)凸患者術(shù)后雙肩美學(xué)平衡。第2節(jié)Lenke 1型青少年特發(fā)性脊柱側(cè)凸前路矯形術(shù)后胸椎后凸角改變與脊柱后份生長的相關(guān)性研究目的：評估Lenke 1型青少年特發(fā)性脊柱側(cè)凸患者前路矯形手術(shù)術(shù)后脊柱前柱和后份生長的情況,進一步探究術(shù)后胸椎后凸角改變的原因。方法：選取2002年6月至2006年11月間在我院接受前路選擇性胸彎固定治療的青少年特發(fā)性脊柱側(cè)凸患者40例,平均年齡14.1±1.7歲。根據(jù)其術(shù)前Risser征分為3組：A組,Risser 0; B組,Risser 1-3;C組,Risser 4～5。在術(shù)前、術(shù)后早期(術(shù)后3-6月)以及末次隨訪時的站立位全脊柱正側(cè)位X線片上測量以下參數(shù)：冠狀面上測量胸彎、腰彎Cobb角；矢狀面上測量：胸椎后凸角(thoracic kyphosis, TK), T5-12各椎體前壁高度(VBHa)、后壁高度(VBHp)、椎弓根高度(PH)及椎弓根間隙高度(IPH)并分別其T5-12的總和SVBHa、 SVBHp、SPH及SIPH。結(jié)果：三組患者例數(shù)分別為：A組：7例；B組：14例；C組19例�；颊咝g(shù)前、術(shù)后、末次隨訪胸椎后凸角分別為10.4�！�12.2。,15.1。土8.6。,18.1�！�6.5。。末次隨訪胸椎后凸角相比術(shù)后3月有增大的趨勢,但差異不顯著。三組中A、B兩組胸椎后凸角較術(shù)后3月分別增大了8.3。、2.2。。A組中SVBHp/SVBHa及(SIPH+SPH)/SVBHa、B組中(SIPH+SPH)/SVBHa在末次隨訪時較術(shù)后3月顯著增加,而B組SVBHp/SVBHa、C組病例SVBHp/SVBHa及(SIPH+SPH)/SVBHa末次隨訪與術(shù)后3月相比無顯著差異。結(jié)論：胸彎青少年特發(fā)性脊柱側(cè)凸患者前路胸椎矯形術(shù)后有前柱生長停滯,后份繼續(xù)生長的現(xiàn)象,從而導(dǎo)致術(shù)后隨訪過程中胸椎后凸在一定時間內(nèi)持續(xù)增大。第3節(jié)Lenke 5型AIS患者前路與后路矯形術(shù)后矢狀面形態(tài)的比較分析目的分析Lenke5型青少年特發(fā)性脊柱側(cè)凸(AIS)患者前路/后路矯形術(shù)后脊柱矢狀面形態(tài)的變化,探討比較不同入路對脊柱矢狀面形態(tài)的影響。方法2005年1月至2010年12月在我科行胸腰/腰椎矯形術(shù)且有完整隨訪資料(隨訪12年)的Lenke5型AIS患者共49例,其中,前路手術(shù)組(A組)23例,后路手術(shù)組(B組)26例。對這兩組患者術(shù)前、術(shù)后早期、術(shù)后1年及末次隨訪的胸腰/腰彎Cobb角、胸彎Cobb角,胸椎后凸角(TK)、腰椎前凸角(LL)和內(nèi)固定近端交界角(PJA)等指標進行測量并進行統(tǒng)計學(xué)分析。結(jié)果A、B兩組的手術(shù)年齡、Risser征、術(shù)前代償胸彎、胸腰/腰彎Cobb角、主彎累及節(jié)段等一般資料均無統(tǒng)計學(xué)差異(P0.05)。A、B兩組術(shù)前矢狀面參數(shù)：TK:15.1° vs.15.6°、 LL:-51.9° vs.-50.3°、PJA:4.7°、vs.4.0°,也均未表現(xiàn)出統(tǒng)計學(xué)差異(P0.05)。A組與B組融合節(jié)段相似,術(shù)后及隨訪兩組繼發(fā)胸彎和主胸腰/腰彎矯形效果也均類似(P0.05)。術(shù)后矢狀面參數(shù)：A組TK較術(shù)前增加0.80,B組TK增幅較大(4.80),B組TK顯著高于A組(P0.05)；A組LL減小6.60,B組LL減小1°；A組PJA稍有增加(0.2。),B組PJA增加2.9。,兩組間LL及PJA均未見顯著性差異(P0.05)。A組平均隨訪2.8±0.9年,B組平均隨訪2.3±0.5年。A、B兩組TK、LL和PJA在術(shù)后1年及末次隨訪均較術(shù)后有小幅增加,B組TK值顯著高于A組(P0.05),其余參數(shù)兩組間未見統(tǒng)計學(xué)差異(P0.05)。結(jié)論Lenke5型AIS行選擇性胸腰腰彎矯形內(nèi)固定術(shù)時,前路與后路手術(shù)均可獲得良好的冠狀面矯形效果。矢狀面上：后路較前路對胸椎后凸恢復(fù)更好,因此,后路手術(shù)對矢狀面形態(tài)重建的效果較前路手術(shù)好。第4節(jié) 嚴重脊柱畸形患者術(shù)前Halo重力牽引后骨密度變化及其相關(guān)因素分析目的：對于嚴重的脊柱畸形,Halo重力牽引是目前應(yīng)用最廣泛的術(shù)前治療手段之一,然而其對于患者骨密度的影響目前尚未見報道。因此本研究以接受術(shù)前Halo重力牽引的嚴重脊柱畸形患者為研究對象,分析其牽引后的骨密度(bone mineral density, BMD)變化情況及相關(guān)影響因素。方法：前瞻性收集了在南京鼓樓醫(yī)院脊柱外科接受至少2月術(shù)前Halo重力牽引治療的嚴重脊柱畸形患者。牽引前和牽引結(jié)束后脊柱矯形手術(shù)前通過雙能X線吸收測量法(dual energy X-ray absorptiometry, DEXA)測定并記錄患者腰椎(L2-L4)和非優(yōu)勢側(cè)股骨頸骨密度。記錄患者的牽引時間、最大牽引重量、牽引前后主彎Cobb角以及患者年齡、性別、病因等基本信息。通過配對t檢驗比較牽引前和牽引結(jié)束后患者的骨密度。通過卡方檢驗比較牽引前后研究人群中骨質(zhì)疏松的發(fā)生率。利用獨立t檢驗、單因素方差分析和Pearson相關(guān)性分析探究與患者骨密度變化的相關(guān)因素。結(jié)果：一共入選20例病例,平均年齡16.3±7.6歲。平均牽引時間為77.9±13.0天,平均最大牽引重量為體重的39.9%±11.1%。與牽引前相比,牽引結(jié)束后17例(85%)患者的腰椎骨密度和18例(90%)患者的非優(yōu)勢側(cè)股骨頸骨密度都發(fā)生了顯著降低。牽引結(jié)束后75%的患者有骨質(zhì)疏松,其發(fā)生率高于牽引前(35%),且差異具有統(tǒng)計學(xué)意義(P0.05)。通過Pearson相關(guān)性分析發(fā)現(xiàn)骨密度降低值僅與牽引時間長短具有相關(guān)性(股骨頸：r=0.581,P=0.012；腰椎：r=0.558,P=0.020)。結(jié)論：接受2月以上術(shù)前Halo重力牽引的嚴重脊柱畸形患者的腰椎和非優(yōu)勢側(cè)股骨頸骨密度牽引結(jié)束后可發(fā)生顯著減少,其減少值與牽引的時間長短相關(guān),臨床應(yīng)用Halo重力牽引時應(yīng)避免牽引時間過長以防止牽引后骨質(zhì)疏松的發(fā)生。
[Abstract]:Chapter 1 Melatonin levels and the pathogenesis of scoliosis. Section 1 Effects of different doses of melatonin on the incidence of scoliosis in C57BL/6J biped erect mice. Objective: Endogenous melatonin (MT) deficiency is considered to be the most important factor in adolescent idiopathic scoliosis (AIS). Previous studies have reported that low melatonin C57BL/6J has a high incidence of scoliosis in bipedal erect mice. At the same time, continuous and exogenous intraperitoneal injection of melatonin can prevent the occurrence and development of scoliosis. Therefore, the purpose of this study was to explore whether early exogenous melatonin supplementation at different doses could affect the incidence of scoliosis in C57BL/6J bipedal erect mice. Methods: 105 three-week-old female SPF mice were randomly selected and 75 mice were operated on to establish bipedal erect mice models. Quadruped rats were randomly divided into two groups: group A: 15 rats were injected with 0.1ml 10% alcohol/normal saline daily, group B: 15 rats were injected with 0.1ml melatonin solution daily at the dose of 8mg/kg. Biped rats were randomly divided into five groups: group C: 15 rats were injected with 0.1ml 10% alcohol/normal saline daily, group D, E, F, G: 15 rats in each group were injected with O.1m daily. L Melatonin solution, dosage of 4 mg/k, 8 mg/kg, 16 mg/kg, 32 mg/kg. 20 weeks after anesthesia, all the mice were examined with whole spine X-ray. Cobb angle and Cobb angle were measured. Scoliosis was defined as scoliosis. The incidence of scoliosis in each group was recorded and compared. Scoliosis occurred in 3%. Scoliosis occurred in 14 mice (14/15,93.3%) in group C without melatonin injection. Scoliosis occurred in 3 mice (3/15,20%) in group E with melatonin injection. Scoliosis occurred in 1 in group D and 1 in group F (1/15,6.7%) respectively. However, there was no significant difference in the incidence of scoliosis between groups D, E, F and G (P 0.05). Conclusion: Melatonin deficiency plays an important role in the development of scoliosis in C57BL/6J bipedal orthostatic mice. Early intraperitoneal injection of melatonin can significantly reduce the incidence of scoliosis in this model. The incidence of columnar scoliosis and the effect does not depend on the dose of melatonin. Chapter 2 Clinical treatment of scoliosis Whether CCAD can be used to predict shoulder imaging, aesthetic balance and patient and surgeon satisfaction after posterior correction in adolescent idiopathic scoliosis (AIS) patients with Lenke type 1. Methods: A retrospective analysis was performed in our hospital from March 2008 to August 2011. Complete imaging data of 44 female adolescents with idiopathic scoliosis of Lenke type 1, with an average age of 15.1 (+ 1.7 years). CCAD was the difference between the left clavicular thoracic angle (CC A) and the right CC A on the upright radiograph of the whole spine. The shoulder height difference (SHD) was the soft tissue image and phase above the left acromioclavicular joint on the upright radiograph of the whole spine. CCAD and SHD were measured before surgery, after surgery and two years after follow-up. Patients with SHD (>1 cm) at the last follow-up were classified as shoulder imbalance group and SHD (>1 cm) as shoulder balance group. At the last follow-up, SHi 1 cm, SHo 1 cm were defined as inner shoulder and outer shoulder balance, SHi (> 1 cm) was defined as inner shoulder and outer shoulder imbalance, and SHi (> 1 cm) was defined as outer shoulder imbalance. Results: At the last follow-up, 18 patients had bilateral shoulder imbalance and 26 had bilateral shoulder balance. The preoperative CCAD of the patients with bilateral shoulder imbalance was significantly higher than that of the patients with bilateral shoulder imbalance (8.1 +3.9.vs. 3.3 +1.8, P 0.001). According to the satisfaction of patients and surgeons, the preoperative CCAD of patients with dissatisfaction group was significantly higher than that of patients with satisfaction group. ROC curve analysis showed that preoperative CCAD predicted postoperative shoulder imaging imbalance. The diagnostic values of patients with dissatisfaction and surgeons'dissatisfaction were both 5.5.. CCAD can not be used to predict postoperative shoulder aesthetic balance in adolescent idiopathic scoliosis Lenke type 1. Lenke type 1 adolescents Objective: To evaluate the anterior and posterior spinal growth in adolescent idiopathic scoliosis Lenke type 1 patients after anterior spinal surgery, and to explore the causes of postoperative thoracic kyphosis. From November 2006 to November 2006, 40 adolescent patients with idiopathic scoliosis who underwent anterior selective thoracic curvature fixation were divided into three groups according to their preoperative Risser signs: group A, Risser 0; group B, Risser 1-3; group C, Risser 4-5. The total standing spine was preoperatively, early postoperatively (3-6 months) and at the last follow-up. The following parameters were measured on axial and lateral X-ray films: thoracic kyphosis (TK), anterior wall height (VBHa), posterior wall height (VBHp), pedicle height (PH) and intervertebral space height (IPH) on coronal plane and sagittal plane, and the sum of T5-12 and SVBHp, SPH and SIPH. Results: The number of patients in the three groups were: group A: 7 cases; group B: 14 cases; group C: 19 cases. The thoracic kyphosis angle of the patients in group A and B were 10.4. + 12.2., 15.1. soil 8.6., 18.1. + 6.5.. The thoracic kyphosis angle of the patients in the last follow-up was increased, but the difference was not significant. SVBHp/SVBHa and (SIPH+SPH)/SVBHa in group A and (SIPH+SPH)/SVBHa in group B increased significantly at the last follow-up compared with 3 months after surgery, while SVBHp/SVBHa in group B, SVBHp/SVBHa in group C and (SIPH+SPH)/SVBHa in the last follow-up showed no significant difference compared with 3 months after surgery. Section 3 Comparison of sagittal morphology between anterior and posterior approaches in patients with Lenke 5 AIS Objective To analyze anterior/posterior approaches in adolescent idiopathic scoliosis (AIS) patients with Lenke 5. Methods From January 2005 to December 2010, 49 patients with Lenke type 5 AIS underwent thoracolumbar/lumbar orthopedics with complete follow-up data (12 years follow-up), including 23 patients in anterior approach group (group A) and 26 patients in posterior approach group (group B). The Cobb angle, Cobb angle, TK angle, LL angle and PJA angle of thoracolumbar lordosis were measured and analyzed statistically. Results The operative age, Risser sign, preoperative compensatory thoracolumbar bend, Cobb angle of thoracolumbar/lumbar bend, and main bend involvement in group A and B were analyzed statistically. There was no significant difference in the sagittal plane parameters between group A and group B (P 0.05). The sagittal plane parameters of group B: TK: 15.1 degrees vs. 15.6 degrees, LL: - 51.9 degrees vs. - 50.3 degrees, PJA: 4.7 degrees, vs. 4.0 degrees, and there was no significant difference between group A and group B (P 0.05). Postoperative sagittal parameters: TK in group A increased by 0.80, TK in group B increased significantly (4.80), TK in group B was significantly higher than that in group A (P 0.05); LL in group A decreased by 6.60, LL in group B decreased by 1 degree; PJA in group A increased slightly (0.2.) and PJA in group B increased by 2.9. (P 0.05). There was no significant difference in LL and PJA between the two groups (P 0.05). The average follow-up time in group A was 2.8 [0.9 years], and the average follow-up time in group B was 2.3 [.5 years, B] TK, LL and PJA in both groups increased slightly at 1 year and the last follow-up. TK in group B was significantly higher than that in group A (P 0.05). There was no significant difference in other parameters between the two groups (P 0.05). Conclusion Both anterior and posterior approaches can achieve good coronal orthopedic results in Lenke 5 AIS patients undergoing selective thoracolumbar curvature and internal fixation. Posterior approach is better than anterior approach in restoring thoracic kyphosis, so posterior approach is better than anterior approach in reconstructing the sagittal plane. One of the treatment methods, however, the effect on bone mineral density (BMD) of patients with severe spinal deformity after preoperative Halo gravity traction has not been reported so far. Dual energy X-ray absorptiometry (DEXA) was used to measure and record the bone mineral density of the lumbar spine (L2-L4) and the non-dominant femoral neck before and after traction. Time, maximum traction weight, main bend Cobb angle before and after traction, patient's age, sex, etiology and other basic information. Bone mineral density was compared before and after traction by paired t test. The incidence of osteoporosis was compared by chi-square test before and after traction. The incidence of osteoporosis was analyzed by independent t test, one-way ANOVA and Pearson test. Result: A total of 20 patients, with an average age of 16.3 (+ 7.6 years), were enrolled in the study. The average traction time was 77.9 (+ 13.0 days) and the average maximum traction weight was 39.9% (+ 11.1%) of body weight. Compared with pre-traction, the lumbar vertebral bone mineral density of 17 patients (85%) and 18 patients (90%) were not excellent after traction. After traction, 75% of the patients had osteoporosis. The incidence of osteoporosis was higher than that before traction (35%) and the difference was statistically significant (P 58, P = 0.020). Conclusion: The bone mineral density of the lumbar spine and the femoral neck of the non-dominant side of the patients with severe spinal deformity who received Halo gravity traction more than 2 months before the operation can be significantly reduced after the traction. The reduction value is related to the length of the traction. The long traction time should be avoided in the clinical application of Halo gravity traction to prevent osteoporosis after the traction. Happen.
【學(xué)位授予單位】：南京大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R682.3

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