目的 探究瘦素受体过表达状态对双足直立小鼠脊柱侧凸发生发展的影响。方法 选取30只购自维通利华的3周龄雌性C3H小鼠,分为A、B、C 3组,每组10只,A组:对照慢病毒正常小鼠;B组:瘦素受体过表达正常小鼠;C组:瘦素受体过表达双足直立小鼠,C组小鼠麻醉后将小鼠双前肢截肢,并切除鼠尾。术后3d,3组小鼠分别颅内注射对应的慢病毒,随后每周注射两次。20周后,取3组小鼠脑脊液及血清,通过酶联免疫吸附实验(ELISA)检测其中瘦素、可溶性瘦素受体及甲状腺素(T4)水平;行X线检查,观察各组小鼠脊柱侧凸发生率及严重程度;行MicroCT检查,检测各组小鼠骨量丢失程度。组间计量数据采用t检验。结果 ELISA结果表明,瘦素受体过表达后小鼠脑脊液中可溶性瘦素受体(3 543±502、3 542±777)、甲状腺素(21。940±4。387、16。120±2。930)、瘦素(2 644。0±271。8、2 148。0±372。3)含量高于 A 组(2 260。000±67。230、7。633±2。901、809。300±552。000,t=4。385、2。847、4。710、3。564、8。435、5。110,P<0。05)。血清中可溶性瘦素受体(2 444±594、2 214±453)、甲状腺素(2。365±0。696、2。444±0。316)含量明显高于 A 组(742。700±438。100、1。059±0。190,t=3。992、4。043、3。135、6。513,P<0。05)。X 线结果显示 B 组小鼠(14。100±5。672)及 C 组(26。600±4。651)小鼠平均 Cobb 角明显大于 A 组(1。400±0。656,t=3。853、9。293,P<0。05)。且C组小鼠脊柱侧凸发生率高于B组,平均Cobb角高于B组(26。600±4。651 比 14。100±5。672,t=2。952、P<0。05)。MicroCT 结果表明,C 组小鼠骨体积分数降低(0。250±0。026比0。337±0。038,t=-3。250,P<0。05)。结论 瘦素受体过表达会导致小鼠脊柱侧凸发生率及严重程度上升。
Effect of leptin receptor overexpression on the occurrence and development of scoliosis in bipedal upright mice
Objective To investigate the effect of leptin receptor overexpression on the occurrence and development of scoliosis in bipedal upright mice.Methods Totally,30 3-weeks-old female C3H mice purchased from CharlesRiver were divided into 3 groups equally:group A(control lentivirus normal mice);group B(leptin receptor overexpression normal mice);group C(leptin receptor overexpression bipedal up-right mice).After anesthesia,the mice in group C were amputated forelimbs and the tail.On the 3rd day after surgery,the mice were intracranially injected with the corresponding lentivirus,and then injected twice a week.After 20 weeks,the cerebrospinal fluid and serum were collected,and leptin,soluble leptin receptors and thyroxine(T4)were detected by enzyme-linked immunosorbent assay(ELISA).X-ray exami-nation was performed to observe the severity of scoliosis.MicroCT was performed to detect the degree of bone loss.Measurement data between groups were analyzed using t test.Results ELISA showed that after leptin receptor overexpression,soluble leptin receptors(3 543±502,3 542±777),thyroxine(21.940±4.387,16.120±2.930)and leptin(2 644.0±271.8,2 148.0±372.3)in cerebrospinal fluid was significantly higher than in group A(2 260.000±67.230,7.633±2.901,809.300±552.000,t=4.385,2.847,4.710,3.564,8.435,5.110,P<0.05);soluble leptin receptor(2 444±594,2 214±453)and thyroxine(2.365±0.696,2.444±0.316)in serum were higher than those in group A(742.700±438.100,1.059±0.190,t=3.992,4.043,3.135,6.513,P<0.05).X-ray examination showed that the average Cobb angle in group B(14.100±5.672)and group C(26.600±4.651)was significantly greater than in group A(1.400±0.656,t=3.853,9.293,P<0.05).Moreover,the incidence of scoliosis in group C was higher than in group B,and the average Cobb angle in group was greater than in group B(26.600±4.651 vs.14.100±5.672,t=2.952,P<0.05).MicroCT showed that the bone volume fraction in group C was reduced(0.250±0.026 vs.0.337±0.038,t=-3.250,P<0.05).Conclusion Leptin receptor overex-pression can increase the incidence and severity of scoliosis in mice.