中国组织工程研究与临床康复
中國組織工程研究與臨床康複
중국조직공정연구여림상강복
JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH
2007年
36期
7310-7313
,共4页
骨质疏松%大鼠,Sprague-Dawley%二膦酸盐类%骨密度
骨質疏鬆%大鼠,Sprague-Dawley%二膦痠鹽類%骨密度
골질소송%대서,Sprague-Dawley%이련산염류%골밀도
背景:双膦酸盐在临床绝经后妇女骨质疏松症防治中疗效显著,而伊班膦酸钠作为新型双膦酸盐制剂正逐渐成为研究热点.目的:通过观察卵巢切除大鼠骨量丢失的相关指标,探讨伊班膦酸钠干预卵巢切除大鼠骨质疏松的有效性,并与尼尔雌醇比较.设计:完全随机分组,对照动物实验.单位:复旦大学医学院骨代谢研究室.材料:选用SD雌性大鼠40只,鼠龄10~12个月.伊班膦酸钠由江苏原子医学研究所国家重点实验室提供.尼尔雌醇由上海第十二制药厂生产.方法:实验于1996-08/1998-06在上海医科大学放射医学研究所骨代谢研究室完成.采用随机抽签法分为4组,每组10只.假手术组:仅切除卵巢周围小块脂肪组织,手术3个月后每天灌胃生理盐水1 mL/只;卵巢切除组、卵巢切除+伊班膦酸钠组、卵巢切除+尼尔雌醇组:均行双侧卵巢切除,3个月后分别开始灌服生理盐水、伊班膦酸钠0.5 mg/(kg·d)水溶物、尼尔雌醇混悬液1 mg/(kg·次).给药组均于给药第1周灌药2次,以后每周1次,均给药90 d.主要观察指标:取左侧股骨,测其干重、灰重,采用PE23110型原子吸收分光光度计测定骨钙含量.采用DPX-L型骨密度测定全身骨密度;采用SPA型单光子大鼠骨密度仪测右侧股骨全长1/2交界处的骨密度.采用AG22020 KNA型万能材料试验机测定股骨抗弯力.采用动力学法由ENCORⅡ型自动生化分析仪测定血碱性磷酸酶活性,采用EDTA滴定法测定尿钙,采用苦味酸法测定尿肌酐;采用改良血尿羟脯氨酸测定法测定尿羟脯氨酸.计算骨小梁面积.结果:大鼠40只均进入结果分析.①骨干重、灰重和钙含量的改变:卵巢切除组大鼠骨干重、灰重和钙含量明显低于其他3组(t=13.58~52.98,P<0.05).②股骨骨密度、抗弯力和全身骨密度的改变:卵巢切除组大鼠股骨骨密度和全身骨密度明显低于其他3组(t=3.31~5.61,P<0.05),而抗弯力与其他3组相近(P>0.05).③血碱性磷酸酶及尿羟脯氨酸与肌酐、钙与肌酐比值的改变:卵巢切除+伊班膦酸钠组和卵巢切除+尼尔雌醇组大鼠尿钙与肌酐比值明显低于卵巢切除组(t=4.04,3.30,P<0.05),其他2项指标在各组间比较,差异无显著性意义(P>0.05).④椎骨、胫骨骨小梁面积的改变:卵巢切除组大鼠椎骨骨小梁面积明显小于其他3组(t=2.22,2.41,3.45,P<0.05),而胫骨骨小梁面积仅卵巢切除+尼尔雌醇组明显大于卵巢切除组(t=2.45,P<0.05).结论:SD大鼠卵巢切除3个月后出现明显的骨质疏松,伊班膦酸钠对卵巢切除骨质疏松模型大鼠骨量的丢失有显著抑制作用,且与尼尔雌醇作用相当.
揹景:雙膦痠鹽在臨床絕經後婦女骨質疏鬆癥防治中療效顯著,而伊班膦痠鈉作為新型雙膦痠鹽製劑正逐漸成為研究熱點.目的:通過觀察卵巢切除大鼠骨量丟失的相關指標,探討伊班膦痠鈉榦預卵巢切除大鼠骨質疏鬆的有效性,併與尼爾雌醇比較.設計:完全隨機分組,對照動物實驗.單位:複旦大學醫學院骨代謝研究室.材料:選用SD雌性大鼠40隻,鼠齡10~12箇月.伊班膦痠鈉由江囌原子醫學研究所國傢重點實驗室提供.尼爾雌醇由上海第十二製藥廠生產.方法:實驗于1996-08/1998-06在上海醫科大學放射醫學研究所骨代謝研究室完成.採用隨機抽籤法分為4組,每組10隻.假手術組:僅切除卵巢週圍小塊脂肪組織,手術3箇月後每天灌胃生理鹽水1 mL/隻;卵巢切除組、卵巢切除+伊班膦痠鈉組、卵巢切除+尼爾雌醇組:均行雙側卵巢切除,3箇月後分彆開始灌服生理鹽水、伊班膦痠鈉0.5 mg/(kg·d)水溶物、尼爾雌醇混懸液1 mg/(kg·次).給藥組均于給藥第1週灌藥2次,以後每週1次,均給藥90 d.主要觀察指標:取左側股骨,測其榦重、灰重,採用PE23110型原子吸收分光光度計測定骨鈣含量.採用DPX-L型骨密度測定全身骨密度;採用SPA型單光子大鼠骨密度儀測右側股骨全長1/2交界處的骨密度.採用AG22020 KNA型萬能材料試驗機測定股骨抗彎力.採用動力學法由ENCORⅡ型自動生化分析儀測定血堿性燐痠酶活性,採用EDTA滴定法測定尿鈣,採用苦味痠法測定尿肌酐;採用改良血尿羥脯氨痠測定法測定尿羥脯氨痠.計算骨小樑麵積.結果:大鼠40隻均進入結果分析.①骨榦重、灰重和鈣含量的改變:卵巢切除組大鼠骨榦重、灰重和鈣含量明顯低于其他3組(t=13.58~52.98,P<0.05).②股骨骨密度、抗彎力和全身骨密度的改變:卵巢切除組大鼠股骨骨密度和全身骨密度明顯低于其他3組(t=3.31~5.61,P<0.05),而抗彎力與其他3組相近(P>0.05).③血堿性燐痠酶及尿羥脯氨痠與肌酐、鈣與肌酐比值的改變:卵巢切除+伊班膦痠鈉組和卵巢切除+尼爾雌醇組大鼠尿鈣與肌酐比值明顯低于卵巢切除組(t=4.04,3.30,P<0.05),其他2項指標在各組間比較,差異無顯著性意義(P>0.05).④椎骨、脛骨骨小樑麵積的改變:卵巢切除組大鼠椎骨骨小樑麵積明顯小于其他3組(t=2.22,2.41,3.45,P<0.05),而脛骨骨小樑麵積僅卵巢切除+尼爾雌醇組明顯大于卵巢切除組(t=2.45,P<0.05).結論:SD大鼠卵巢切除3箇月後齣現明顯的骨質疏鬆,伊班膦痠鈉對卵巢切除骨質疏鬆模型大鼠骨量的丟失有顯著抑製作用,且與尼爾雌醇作用相噹.
배경:쌍련산염재림상절경후부녀골질소송증방치중료효현저,이이반련산납작위신형쌍련산염제제정축점성위연구열점.목적:통과관찰란소절제대서골량주실적상관지표,탐토이반련산납간예란소절제대서골질소송적유효성,병여니이자순비교.설계:완전수궤분조,대조동물실험.단위:복단대학의학원골대사연구실.재료:선용SD자성대서40지,서령10~12개월.이반련산납유강소원자의학연구소국가중점실험실제공.니이자순유상해제십이제약엄생산.방법:실험우1996-08/1998-06재상해의과대학방사의학연구소골대사연구실완성.채용수궤추첨법분위4조,매조10지.가수술조:부절제란소주위소괴지방조직,수술3개월후매천관위생리염수1 mL/지;란소절제조、란소절제+이반련산납조、란소절제+니이자순조:균행쌍측란소절제,3개월후분별개시관복생리염수、이반련산납0.5 mg/(kg·d)수용물、니이자순혼현액1 mg/(kg·차).급약조균우급약제1주관약2차,이후매주1차,균급약90 d.주요관찰지표:취좌측고골,측기간중、회중,채용PE23110형원자흡수분광광도계측정골개함량.채용DPX-L형골밀도측정전신골밀도;채용SPA형단광자대서골밀도의측우측고골전장1/2교계처적골밀도.채용AG22020 KNA형만능재료시험궤측정고골항만력.채용동역학법유ENCORⅡ형자동생화분석의측정혈감성린산매활성,채용EDTA적정법측정뇨개,채용고미산법측정뇨기항;채용개량혈뇨간포안산측정법측정뇨간포안산.계산골소량면적.결과:대서40지균진입결과분석.①골간중、회중화개함량적개변:란소절제조대서골간중、회중화개함량명현저우기타3조(t=13.58~52.98,P<0.05).②고골골밀도、항만력화전신골밀도적개변:란소절제조대서고골골밀도화전신골밀도명현저우기타3조(t=3.31~5.61,P<0.05),이항만력여기타3조상근(P>0.05).③혈감성린산매급뇨간포안산여기항、개여기항비치적개변:란소절제+이반련산납조화란소절제+니이자순조대서뇨개여기항비치명현저우란소절제조(t=4.04,3.30,P<0.05),기타2항지표재각조간비교,차이무현저성의의(P>0.05).④추골、경골골소량면적적개변:란소절제조대서추골골소량면적명현소우기타3조(t=2.22,2.41,3.45,P<0.05),이경골골소량면적부란소절제+니이자순조명현대우란소절제조(t=2.45,P<0.05).결론:SD대서란소절제3개월후출현명현적골질소송,이반련산납대란소절제골질소송모형대서골량적주실유현저억제작용,차여니이자순작용상당.
BACKGROUND: Diphosphonate has a predominant therapeutic effect in the prevention and treatment of postmenopausal osteoporosis. Ibandronate, as a new-type diphosphonate preparation, is gradually becoming a study hotspot.OBJECTIVE: This study is to investigate the efficiency of ibandronate in interfering postmenopausal osteoposis by observing bone mass loss related indexes in ovariectomized rats, and made a comparison with nilestriol.DESIGN: A completely randomized grouping, and controlled animal experiment.SETTING: Study Room for Bone metabolism, Fudan University Medical College.MATERIALS: Forty SD female rats, aged 10-12 months, were involved in this study. Ibandronate was provided by the State Key Laboratory of Jiangsu Institute of Atomic Medicine. Nilestriol was produced in the Shanghai 12th Pharmaceutical Factory.METHODS: This experiment was carried out in the Study Room for Bone Metabolism, Institute of Radiation Medicine,Shanghai Medical University between August 1996 and June 1998. The rats were divided into 4 groups by a lot, 10 rats in each: sham-operation group, ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group. In the sham-operation group, only small pieces of adipose tissue around the ovary were resected from the rats.Three months after operation, each rat was intragastrically administrated with 1 mL normal saline; In the ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group, each rat was subjected to bilateral ovariectomy, and 3 months later, they were intragastrically administrated with normal saline, ibandronate water solution [0.5 mg/( kg·d)] and nilestriol suspension [1 mg/(kg· time)] respectively. Each rat in the latter three groups was administrated for 90 days, twice in the first week, and then once a week.MAIN OUTCOME MEASURES: Left femur was taken out, and its dry weight and ash weight were measured. Calcium content of bone was determined with an atomic absorption spectrophotometer, bone density of the whole body with a bone density apparatus, the bone density at the juncture of 1/2 right femoral bone length with a single photon bone density apparatus, and femoral anti-bending force was determined with a universal testing machine. Alkaline phosphatase were determined by dynamical method with an automatic biochemistry analyzer, urine calcium by EDTA titration method, urine creatinine by picric kinetic method, and urinary hydroxyproline by modified proline assay.Trabecular area was calculated.RESULTS: Forty rats were involved in the final analysis. ① Bone dry weight, bone ash weight and bone calcium content in the ovariectomized group were significantly lower than those in the other 3 groups, respectively (t =13.58-52.98, P <0.05). ② Femoral bone density and bone density of the whole body of rats in the ovariectomized group were significantly lower than those in the other 3 groups (t =3.31-5.61, P<0.05), while anti-bending force was close between ovariectomized group and the other 3 groups (P>0.05). ③ The ratio of urine calcium to urine creatinine was significantly lower in the ovariectomized+ibandronate group and ovariectomized +nilestriol group than in the ovariectomized group (t =4.04, 3.30, P<0.05). No significant difference in the alkaline phosphatase and ratio of urinary hydroxyproline to urinary creatinine existed among the groups (P > 0.05). ④Trabecular area of vertebrae in the ovariectomized group was significantly smaller than that in the other 3 groups (t =2.22,2.41,3.45,P < 0.05), while the trabecular area of tibia in the ovariectomized group was only smaller than that in the ovariectomized +nilestriol group (t =2.45, P< 0.05).CONCLUSION: Osteoporosis apPears obviously in the SD rats 3 months after ovariectomy. Ibandronate has obviously inhibitory effects on the bone mass loss of rats with postmenopausal osteoposis, and it is equivalent to nilestriol in inhibitory effect.