中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2010年
2期
99-103
,共5页
贾红蔚%崔瑾%张鑫%雒瑢%邱明才
賈紅蔚%崔瑾%張鑫%雒瑢%邱明纔
가홍위%최근%장흠%락용%구명재
糖尿病,实验性%骨形态计量学%实时定量聚合酶链反应%RANK配体%骨保护素%核结合因子1%Osterix%骨钙素%Ⅰ型胶原氨基末端交联肽
糖尿病,實驗性%骨形態計量學%實時定量聚閤酶鏈反應%RANK配體%骨保護素%覈結閤因子1%Osterix%骨鈣素%Ⅰ型膠原氨基末耑交聯肽
당뇨병,실험성%골형태계량학%실시정량취합매련반응%RANK배체%골보호소%핵결합인자1%Osterix%골개소%Ⅰ형효원안기말단교련태
Diabetic mellitas,experimental%Bone histomorpbometry%Real-time quantitative polymerase reaction%RANK ligand%Osteoprotegerin%Core binding factor 1%Osterix%Osteocalcin%Cross-linked N-telopeptide of typelcollagen
目的 探讨链脲佐菌素(STZ)诱导的糖尿病大鼠骨转换变化及其分子机制.方法 单次尾静脉注射STZ制造糖尿病大鼠模型.成模后与正常对照组大鼠同步饲养8周,处死后测定两组大鼠血钙、磷、碱性磷酸酶、骨钙素、24 h尿钙水平和尿I型胶原氨基末端交联肽(NTx)/肌酐(Cr)比值,双能X线吸收法(DEXA)测定大鼠离体腰椎和股骨骨密度.骨形态计量学方法分析大鼠骨量和骨转换变化情况,并用实时荧光定量RT-PCR方法检测骨组织中标志骨吸收的NF-κB受体活化因子配体(RANKL)/骨保护素mRNA比值和标志骨形成的骨钙素以及调控成骨的核结合因子1(Cbfa1)、osterix(OSX)mRNA表达水平.结果 与正常对照组相比,糖尿病大鼠血钙、磷、碱性磷酸酶水平无显著差异,骨钙素水平显著减低[(3.03±0.52)对(6.18±0.71)ng/ml,P<0.01],24 h尿钙水平显著增加[(16.84±0.71)对(4.98±0.58)mg/24 h,P<0.01],尿NTx/Cr比值显著下降[(5.67±0.86)对(5.23±0.98)nmol/g Cr,P<0.05].糖尿病大鼠腰椎骨密度显著减低[(0.107±0.011)对(0.149±0.009)g/cm~3,P<0.01],股骨骨密度亦显著减低[(0.099±0.013)对(0.139±0.013)g/cm~3,P<0.01].骨形态计量学分析提示糖尿病大鼠骨小梁骨量减少,骨小梁矿化表面减少,骨形成速率减低[(0.44±0.11)对(0.78±0.14)μm/d,P<0.01].实时荧光定量RT-PCR提示糖尿病大鼠骨组织中RANKL/骨保护素mRNA比值[(0.57±0.11)对(0.89±0.13),P<0.01]、骨钙素[(2.25×10~(-4)±1.19×10~(-4))对(3.43×10~(-4)±1.63×10~(-4)),P<0.01]、Cbfa1[(26.68×10~(-4)±6.53×10~(-4))对(37.21×10~(-4)±7.14×10~(-4)),P<0.01]、OSX[(1.93×10~(-4)±0.65×10~(-4))对(4.19×10~(-4)±0.71×10~(-4)),P<0.01]mRNA水平均较正常对照组显著减低.结论 糖尿病大鼠是一种低转换型骨量减少,其骨组织中调控破骨的RANKL/骨保护素mRNA水平和调控成骨的Cbfa1、OSX、骨钙素mRNA水平均下降.
目的 探討鏈脲佐菌素(STZ)誘導的糖尿病大鼠骨轉換變化及其分子機製.方法 單次尾靜脈註射STZ製造糖尿病大鼠模型.成模後與正常對照組大鼠同步飼養8週,處死後測定兩組大鼠血鈣、燐、堿性燐痠酶、骨鈣素、24 h尿鈣水平和尿I型膠原氨基末耑交聯肽(NTx)/肌酐(Cr)比值,雙能X線吸收法(DEXA)測定大鼠離體腰椎和股骨骨密度.骨形態計量學方法分析大鼠骨量和骨轉換變化情況,併用實時熒光定量RT-PCR方法檢測骨組織中標誌骨吸收的NF-κB受體活化因子配體(RANKL)/骨保護素mRNA比值和標誌骨形成的骨鈣素以及調控成骨的覈結閤因子1(Cbfa1)、osterix(OSX)mRNA錶達水平.結果 與正常對照組相比,糖尿病大鼠血鈣、燐、堿性燐痠酶水平無顯著差異,骨鈣素水平顯著減低[(3.03±0.52)對(6.18±0.71)ng/ml,P<0.01],24 h尿鈣水平顯著增加[(16.84±0.71)對(4.98±0.58)mg/24 h,P<0.01],尿NTx/Cr比值顯著下降[(5.67±0.86)對(5.23±0.98)nmol/g Cr,P<0.05].糖尿病大鼠腰椎骨密度顯著減低[(0.107±0.011)對(0.149±0.009)g/cm~3,P<0.01],股骨骨密度亦顯著減低[(0.099±0.013)對(0.139±0.013)g/cm~3,P<0.01].骨形態計量學分析提示糖尿病大鼠骨小樑骨量減少,骨小樑礦化錶麵減少,骨形成速率減低[(0.44±0.11)對(0.78±0.14)μm/d,P<0.01].實時熒光定量RT-PCR提示糖尿病大鼠骨組織中RANKL/骨保護素mRNA比值[(0.57±0.11)對(0.89±0.13),P<0.01]、骨鈣素[(2.25×10~(-4)±1.19×10~(-4))對(3.43×10~(-4)±1.63×10~(-4)),P<0.01]、Cbfa1[(26.68×10~(-4)±6.53×10~(-4))對(37.21×10~(-4)±7.14×10~(-4)),P<0.01]、OSX[(1.93×10~(-4)±0.65×10~(-4))對(4.19×10~(-4)±0.71×10~(-4)),P<0.01]mRNA水平均較正常對照組顯著減低.結論 糖尿病大鼠是一種低轉換型骨量減少,其骨組織中調控破骨的RANKL/骨保護素mRNA水平和調控成骨的Cbfa1、OSX、骨鈣素mRNA水平均下降.
목적 탐토련뇨좌균소(STZ)유도적당뇨병대서골전환변화급기분자궤제.방법 단차미정맥주사STZ제조당뇨병대서모형.성모후여정상대조조대서동보사양8주,처사후측정량조대서혈개、린、감성린산매、골개소、24 h뇨개수평화뇨I형효원안기말단교련태(NTx)/기항(Cr)비치,쌍능X선흡수법(DEXA)측정대서리체요추화고골골밀도.골형태계량학방법분석대서골량화골전환변화정황,병용실시형광정량RT-PCR방법검측골조직중표지골흡수적NF-κB수체활화인자배체(RANKL)/골보호소mRNA비치화표지골형성적골개소이급조공성골적핵결합인자1(Cbfa1)、osterix(OSX)mRNA표체수평.결과 여정상대조조상비,당뇨병대서혈개、린、감성린산매수평무현저차이,골개소수평현저감저[(3.03±0.52)대(6.18±0.71)ng/ml,P<0.01],24 h뇨개수평현저증가[(16.84±0.71)대(4.98±0.58)mg/24 h,P<0.01],뇨NTx/Cr비치현저하강[(5.67±0.86)대(5.23±0.98)nmol/g Cr,P<0.05].당뇨병대서요추골밀도현저감저[(0.107±0.011)대(0.149±0.009)g/cm~3,P<0.01],고골골밀도역현저감저[(0.099±0.013)대(0.139±0.013)g/cm~3,P<0.01].골형태계량학분석제시당뇨병대서골소량골량감소,골소량광화표면감소,골형성속솔감저[(0.44±0.11)대(0.78±0.14)μm/d,P<0.01].실시형광정량RT-PCR제시당뇨병대서골조직중RANKL/골보호소mRNA비치[(0.57±0.11)대(0.89±0.13),P<0.01]、골개소[(2.25×10~(-4)±1.19×10~(-4))대(3.43×10~(-4)±1.63×10~(-4)),P<0.01]、Cbfa1[(26.68×10~(-4)±6.53×10~(-4))대(37.21×10~(-4)±7.14×10~(-4)),P<0.01]、OSX[(1.93×10~(-4)±0.65×10~(-4))대(4.19×10~(-4)±0.71×10~(-4)),P<0.01]mRNA수평균교정상대조조현저감저.결론 당뇨병대서시일충저전환형골량감소,기골조직중조공파골적RANKL/골보호소mRNA수평화조공성골적Cbfa1、OSX、골개소mRNA수평균하강.
Objective To study the bone turnover and its related molecular mechanism in STZ-induced diabetic rats. Methods Of 30 male SD rats studied, 15 were induced diabetics by intravenous injection of streptozotocin (50 mg/kg)and fed for 8 weeks. After the sacrifice of both the diabetic and control groups, serum Ca, P, alkaline phosphatase (ALP), and osteocalcin were determined, and 24 h urinary Ca and urinary cross-linked N-telopeptide of type Ⅰ collagen (NTx)and creatinine (Cr)ratio were also determined. The left tibia was dissected for bone histomorphometry analysis. Right femur and lumbar vertebrae (L1-L4) were reserved for bone mineral density (BMD) determination. The right tibia was separated for the study of bone tissue RANKL/osteoprotegerin, Core binding factor 1 (Cbfa1) ,osterix and osteocalcin mRNA level which was performed by real-time quantitative reverse transcription polymerase chain reaction assay. Results No significant difference was found in serum Ca, P, and ALP levels between 2 groups of rats. ST-Z-induced diabetic rats were characterized by extreme hyperglycemia, marked weight loss, polyuria, and hypercalciuria. A low-turnover osteopenia was evidenced in diabetic rats by decreased BMD in both femur [(0. 099±0.013) vs (0. 139 ± 0.013 g/cm~3) , P < 0.01] and lumbar vertebrae [(0. 107±0.011)vs (0. 149±0.009) g/cm~3, P<0.01] , reduced serum osteoealcin level [a marker of formation, (3.03±0.52) vs (6. 18±0.71) ng/ml ,P<0. 01]) ,decreased urine NTx/Cr ratio [(5. 67±0.86) vs (5.23±0.98) nmol/g Cr, P<0. 05], decreased trabeeular volume and thickness, and reduced bone label surface and bone formation rate [(0. 44±0. 11) vs (0. 78±0. 14) μm/d,P<0. 01] by bone dynamic study. The RANKL/ osteoprotegerin [(0.57±0.11)vs (0.89±0.13) ,P<0.01] ,osterix [(1.93×10~(-4)±0.65×10(~-4))vs (4.19×10~(-4)± 0.71×10~(-4)) ,P<0.01] ,Cbfa1 [(26.68×10~(-4)±6.53×10~(-4))vs (37.21×10~(-4)±7.14×10~(-4)) ,P<0.01] ,and osteocalcin [(2.25×10~(-4)±1.19×10~(-4))vs (3.43×10~(-4)±1.63×10~(-4)) ,P<0.01] mRNA expressions were declined in the bone tissue of the tibia in the ST-Z-induced diabetic rats, as compared with the control. Conclusion A low-turnover osteopenia is evidenced in STZ-induced diabetic rats by significant decrease of both osteoclastic marker(RANKL/ osteoprotegerin)and osteoblastic marker (osterix ,Cbfa1 ,osteocalcin)mRNA levels in tibia.
