颅脑创伤致瘦素渗漏人脑促进骨折愈合的实验研究

Experimental study on promotion of fracture healing caused by leptin leaking into brain after craniocerebral trauma

目的观察兔颅脑创伤后血清瘦素、生长激素、胰岛素样生长因子-1水平及脑脊液瘦素水平。方法15只兔麻醉后血管内注射外源性异硫氰酸荧光素标记的兔瘦素，分别给予单侧液压打击致颅脑创伤（9只）及假手术（6只），伤后30min取双侧脑组织行冰冻切片，荧光显微镜下观察颅脑创伤组和假手术组脑组织荧光范围。33只兔随机分为实验组（血）、对照组（血）、实验组（脑脊液）和对照组（脑脊液），实验组建立兔脑单侧液压打击创伤模型，对照组只开骨窗。实验组（血）和对照组（血）均于伤后第1、3、7和14天早晨空腹取耳缘静脉血2ml，分离血清；实验组（脑脊液）和对照组（脑脊液）均于上述各时间点取脑脊液0．5ml；采用ELISA法检测血清瘦素、生长激素、胰岛素样生长因子-1水平和脑脊液瘦素水平。结果颅脑创伤组打击侧脑组织在荧光显微镜下可见到荧光显影，多于假手术组。实验组颅脑创伤后各时间点血清瘦素水平均高于对照组；实验组血清生长激素、胰岛素样生长因子-1及脑脊液瘦素水平在颅脑创伤后第1、3和7天均高于对照组。结论颅脑创伤后血液内瘦素能渗漏入脑组织，引起血液内生长激素及胰岛素样生长因子-1浓度增加，可能是颅脑创伤促进骨折愈合的内分泌因素。

Objective To observe whether rabbit blood leptin can leak into the brain after craniocerebral trauma （CCT）, and to dynamically detect serum levels of leptin, growth hormone （GH）, and insulinlike growth factor-1 （IGF-1）, and leptin level in cerebrospinal fluid （CSF） after CCT. Methods The FITC labeled leptin was injected into blood vessels of 15 adult male rabbits after anesthesia. Then 9 rabbits underwent unilateral fluid percussive impact, while 6 rabbits underwent sham operation. Thirty minutes postoperatively, brain tissue was taken to make frozen sections which were used to observe fluorescence labeled leptin range. Thirty three adult male rabbits were randomly divided into serum group, serum-control group, CSF group and CSF-control group. Rabbits in serum group and CSF group received fluid percussive impact, while rabbits in serum-control group and CSF-control group were drilled a 7 mm window in skull. Rabbits in serum group and serum-control group were phlebotomized 2 ml at 1 d, 3 d, 7 d and 14 d after operation, and rabbits in CSF group and CSF-control group were extracted CSF 0.5 ml at the same time points. Then serum levels of leptin, GH, and IGF-1, and leptin level in CSF were tested by ELISA. Results The fluorescence imaging could be seen in the injured brain tissue of rabbits with CCT, which was more than those in brain tissue of rabbits receiving sham operation. Serum leptin levels of rabbits in serum group at each time point were high- er than those in serum-control group. Serum levels of GH and IGF-1 and leptin level in CSF were higher in rabbits with CCT than those in rabbits without CCT at 1 d, 3 d and 7 d after operation. Conclusion The blood leptin can leak into the brain after CCT, which can cause increase of blood GH and IGF-1. And the latter may be the endocrine factors promoting fracture healing after CCT.