模拟失重大鼠牙体牙髓牙周组织的变化研究
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摘要
失重是航空航天过程中人类必须面临和克服的问题。已有的研
究表明，失重可导致心血管系统，骨骼系统、免疫系统等的生理甚
至病理改变，但目前在实际的航天飞行过程中进行各种医学实验，
由于受到种种条件的限制，很难全部展开，大部分实验是在模拟失
重的条件下进行的，其中比较成功的方法是采用尾部悬吊模拟失重
大鼠进行实验，取得一系列研究成果和发现。可是在口腔方面，失
重对牙齿及相关组织影响的研究，国外报道很少，国内未见报道。
为此，我们对尾部悬吊模拟失重大鼠的牙体牙髓牙周组织的变
化进行研究，旨在探讨失重对牙齿及相关组织的影响，试着解释失
重条件下牙齿及相关组织发生生理或病理变化的机制。
本研究采用30只雄性大鼠，按体重配对随机分为模拟失重组，
即悬吊组（suspention组，简称s组）；失重对抗组，即1.5地球引
力组（1.5Gravitation，1.5G组）；正常对照组（control，c组），每组10只
动物。模拟失重组：将鼠的尾部悬吊，使大鼠始终保持30°头低
位及后肢自由悬垂不负荷状态；1.5G对抗组是在悬吊处理的基础
上，每天给予1h的离心对抗措施，使大鼠背胸方向所受加速度为
1.5G。实验周期21d，实验结束时处死动物，常规制作含有牙齿的
上、下颌骨标本，分别进行以下实验。
实验一 模拟失重大鼠牙体牙髓牙周组织的组织形态学变化。
常规制作切片，采用HE和改良Mallory's三色染色法染色。结
论如下：
1．模拟失重条件下牙髓组织出现了较为显著的充血、水肿和
白细胞渗出现象，这可能与牙髓组织所处的特殊的解剖环境有关。
一一
2．1．SG人工重力条件下，牙髓组织也出现了轻度的充血、水
肿变化，说明这种人工重力的对抗措施不足以消除牙髓组织的病纠1
变化。
3．模拟失重对牙周膜和牙槽骨的影响较小，这可能与它们的血
液供给丰富，有较强的代谢补偿能力有关。
4．模拟失重鼠可出现髓腔侧牙体组织的矿化不良，这可能是才
J 髓组织受到影响而导致牙体组织矿化障碍的结果。
5．1．SG对抗措施只能部分改善鼠的牙体组织的矿化程度，此利l
矿化程度受到牙髓状况的影响。
‘实验二二模拟失重人鼠牙体、牙髓、才川组织分L、磷、锌代测
变化。
钙（o）的含量多少是牙体、才槽骨矿化的重要柯忐，磷门’）
和锌（Zn）与碱性磷酸酶的活性密切相关，P又是构成羟基磷灰1｝l
；和有机物的重要元素。本实验采用扫描电镜及能谱分析系统对3组
鼠标本的牙体、牙髓、牙周组织的Ca、P、Zn的相对百分含量进行
检测，旨在考察模拟失重对鼠牙体、牙髓、牙周组织Ca、P、Zn却
代谢和矿化程度的影响及采用相应对抗措施后的防护效果。给论如
下：
1．模拟失重大鼠的丁体组织山于重力作用消失导致了Cd、P。
Zn含量变化，其中Ca的相对百分含量明显下降，而P稍有升高，
Zn的变化不明显，说明失重可能引起牙本质矿化不良。
2．扫描电镜能谱分析方法不适用于对牙髓和牙周组织的CaI
Zn的含量变化分析。
3．模拟失重大鼠的牙槽骨中＊。、P、Zn的含量与正常对照组、
1．5对抗组相比，无显著差异，说明失重环境对牙槽骨的矿化影响不
大。
－4－
第四军医大学硕士学位论文
4．本实验能谱分析所测结果仅反映3组鼠的习’体、牙髓、才
周组织中的＊。、P丸＊n相对含量之变化，并非它们实际含量的改变。
实验三模拟失重大鼠牙体牙髓牙周组织中TGF pl、C－fos
NI、IV型胶原的表达
TGF－DI具有促进成本质细胞形成和分化的功能，是牙本质付
化过程中重要的调节囚于。C－fos是快速反应基囚的一种，起着核内
第三信使的作用，参与细胞的生长、分裂、信息传递等牛理过W。
各种刺激均可诱导 c．fos的表达。胶原蛋白I＊ollagen，col l）Hg【］1
胞外基质的主要成分之一，在牙髓一牙本质复合体和牙周膜的改洼
和修复过程中起着重要作用。胶原IV是基质胶原，呈薄网状存介
于基膜中，是构成血管基底细胞膜等的重要成分。本实验采用免疫
组织化学的人沾，对趾拟大亚鼠才体、才髓、才J，o组织小的细胞卜
于 TGFD，C－fOS和胶原蛋白 1、IV表达特征进行观察，旨在探
讨模拟失重条件下它们在牙体、牙髓、牙周组织中的功能效应，纠
Weightlessness is one of the problems which human must face with and solve during space flight. Previous studies suggested thai weightlessness could cause physiological and pathological changes of cardiovascular system, skeletal system and immune system. Because it was difficult to do these experiments entirely due to some limits, lots of medical experiments were carried out on ground to mimic weightlessness in space. It was a very successful way to mimic weightlessness using tail suspension rats, and have been accomplished many achievements and findings. But there were few reports about the effects of weightlessness on teeth and related tissues aboard, while no report in China in dental field.
Therefore, we studied the changes of dentin, dental pulp and periodontium of simulated weightlessness rats by tail suspension to explore the effects of weightlessness on tooth and related tissues, and tried to elucidate the physiological and pathyological mechanism about the changes of teeth and related tissues under condition of weightlessness.
30 male SD (Sprague-Dewless) rats were used in this study, divided into three groups by body weight randomly, which were suspension group (S group), 1.5G countermeasure group (1.5 gravitation, 1.5G) and control group(C group). Every group had 10 rats. Rats were kept in 30 ?head-lowered tilt by tail suspension. In 1.5G countermeasure group, on the base of suspension, rats were treated with inertial centrifugal force in 1 h/d by rotary system and the acceleration of
back-breast direction is 1.5G in the countermeasure group. The rats were slaughtered at 21 d; alveolar samples containing teeth were routinely prepared.
Three experiments were carried out as following:
1. Morphological changes of dentin, dental pulp and periodontium of simulated weightlessness rats.
Specimens were prepared normally, stained using HE and improved Mallory's method. The following conclusions are:
1.1 In suspension group, dental pulp appeared apparent congestion, edema and leukocyte effusion., this might be related with dental pulp's special anatomical structures.
1.2 In dental pulp, light congestion and dropsy appeared, which suggested that the effect of countermeasure was not enough to eliminate pathological changes of dental pulp.
1.3 Simulated weightlessness had little influence on periodontium and alveolar bone. This might due to their adequate blood supply and strong compensating potential.
1.4 Abnormal mineralization of halfway dentin near dental pulp in suspension group could be observed, which implied that pulp tissues were influenced by weightlessness and resulted in the prohibiting of dentin mineralization
1.5 Artificial countermeasure can only partially improve dentin-mineralized level in part, which was decided by pulp condition. 2. Metabolic changes of Ca, P, Zn in dentin,dental pulp and periodontium of simulated weightlessness rats.
Ca concentration was an important mineralized symbol of dentin
and alveolar bone. P and Zn were closely related with ALP. P was also an important element consisting of hydroxyphosphate crystal and organic materials. The relative percentage of Ca, P, Zn in the dentin, dental pulp and alveolar bone of rats in three groups were analyzed using energy spectrum analysis, to investigate the metabolism of Ca. P, Zn in dentin,pulp,alveolar bones of simulated weightlessness rats, and the protective effect of 1.5G countermeasure.
Results were found as follows:
2.1 The Ca, P, Zn concentration of dentin altered due to weightlessness in simulated weightlessness rats respectively, and the relative percentage of Ca declined significantly. P increased slightly, no apparent changes of Zn were found. It was implied that weightlessness might bring about deformed mineralization.
2.2. The energy spectrum analysis was not fit for the analysis of Ca, P, Zn concentration alteration in dental pulp and alveolar.
2.3 There were no significant differences among three groups about Ca, P, Zn concentration of alveolar bone. It was suggested tha
究表明，失重可导致心血管系统，骨骼系统、免疫系统等的生理甚
至病理改变，但目前在实际的航天飞行过程中进行各种医学实验，
由于受到种种条件的限制，很难全部展开，大部分实验是在模拟失
重的条件下进行的，其中比较成功的方法是采用尾部悬吊模拟失重
大鼠进行实验，取得一系列研究成果和发现。可是在口腔方面，失
重对牙齿及相关组织影响的研究，国外报道很少，国内未见报道。
为此，我们对尾部悬吊模拟失重大鼠的牙体牙髓牙周组织的变
化进行研究，旨在探讨失重对牙齿及相关组织的影响，试着解释失
重条件下牙齿及相关组织发生生理或病理变化的机制。
本研究采用30只雄性大鼠，按体重配对随机分为模拟失重组，
即悬吊组（suspention组，简称s组）；失重对抗组，即1.5地球引
力组（1.5Gravitation，1.5G组）；正常对照组（control，c组），每组10只
动物。模拟失重组：将鼠的尾部悬吊，使大鼠始终保持30°头低
位及后肢自由悬垂不负荷状态；1.5G对抗组是在悬吊处理的基础
上，每天给予1h的离心对抗措施，使大鼠背胸方向所受加速度为
1.5G。实验周期21d，实验结束时处死动物，常规制作含有牙齿的
上、下颌骨标本，分别进行以下实验。
实验一 模拟失重大鼠牙体牙髓牙周组织的组织形态学变化。
常规制作切片，采用HE和改良Mallory's三色染色法染色。结
论如下：
1．模拟失重条件下牙髓组织出现了较为显著的充血、水肿和
白细胞渗出现象，这可能与牙髓组织所处的特殊的解剖环境有关。
一一
2．1．SG人工重力条件下，牙髓组织也出现了轻度的充血、水
肿变化，说明这种人工重力的对抗措施不足以消除牙髓组织的病纠1
变化。
3．模拟失重对牙周膜和牙槽骨的影响较小，这可能与它们的血
液供给丰富，有较强的代谢补偿能力有关。
4．模拟失重鼠可出现髓腔侧牙体组织的矿化不良，这可能是才
J 髓组织受到影响而导致牙体组织矿化障碍的结果。
5．1．SG对抗措施只能部分改善鼠的牙体组织的矿化程度，此利l
矿化程度受到牙髓状况的影响。
‘实验二二模拟失重人鼠牙体、牙髓、才川组织分L、磷、锌代测
变化。
钙（o）的含量多少是牙体、才槽骨矿化的重要柯忐，磷门’）
和锌（Zn）与碱性磷酸酶的活性密切相关，P又是构成羟基磷灰1｝l
；和有机物的重要元素。本实验采用扫描电镜及能谱分析系统对3组
鼠标本的牙体、牙髓、牙周组织的Ca、P、Zn的相对百分含量进行
检测，旨在考察模拟失重对鼠牙体、牙髓、牙周组织Ca、P、Zn却
代谢和矿化程度的影响及采用相应对抗措施后的防护效果。给论如
下：
1．模拟失重大鼠的丁体组织山于重力作用消失导致了Cd、P。
Zn含量变化，其中Ca的相对百分含量明显下降，而P稍有升高，
Zn的变化不明显，说明失重可能引起牙本质矿化不良。
2．扫描电镜能谱分析方法不适用于对牙髓和牙周组织的CaI
Zn的含量变化分析。
3．模拟失重大鼠的牙槽骨中＊。、P、Zn的含量与正常对照组、
1．5对抗组相比，无显著差异，说明失重环境对牙槽骨的矿化影响不
大。
－4－
第四军医大学硕士学位论文
4．本实验能谱分析所测结果仅反映3组鼠的习’体、牙髓、才
周组织中的＊。、P丸＊n相对含量之变化，并非它们实际含量的改变。
实验三模拟失重大鼠牙体牙髓牙周组织中TGF pl、C－fos
NI、IV型胶原的表达
TGF－DI具有促进成本质细胞形成和分化的功能，是牙本质付
化过程中重要的调节囚于。C－fos是快速反应基囚的一种，起着核内
第三信使的作用，参与细胞的生长、分裂、信息传递等牛理过W。
各种刺激均可诱导 c．fos的表达。胶原蛋白I＊ollagen，col l）Hg【］1
胞外基质的主要成分之一，在牙髓一牙本质复合体和牙周膜的改洼
和修复过程中起着重要作用。胶原IV是基质胶原，呈薄网状存介
于基膜中，是构成血管基底细胞膜等的重要成分。本实验采用免疫
组织化学的人沾，对趾拟大亚鼠才体、才髓、才J，o组织小的细胞卜
于 TGFD，C－fOS和胶原蛋白 1、IV表达特征进行观察，旨在探
讨模拟失重条件下它们在牙体、牙髓、牙周组织中的功能效应，纠
Weightlessness is one of the problems which human must face with and solve during space flight. Previous studies suggested thai weightlessness could cause physiological and pathological changes of cardiovascular system, skeletal system and immune system. Because it was difficult to do these experiments entirely due to some limits, lots of medical experiments were carried out on ground to mimic weightlessness in space. It was a very successful way to mimic weightlessness using tail suspension rats, and have been accomplished many achievements and findings. But there were few reports about the effects of weightlessness on teeth and related tissues aboard, while no report in China in dental field.
Therefore, we studied the changes of dentin, dental pulp and periodontium of simulated weightlessness rats by tail suspension to explore the effects of weightlessness on tooth and related tissues, and tried to elucidate the physiological and pathyological mechanism about the changes of teeth and related tissues under condition of weightlessness.
30 male SD (Sprague-Dewless) rats were used in this study, divided into three groups by body weight randomly, which were suspension group (S group), 1.5G countermeasure group (1.5 gravitation, 1.5G) and control group(C group). Every group had 10 rats. Rats were kept in 30 ?head-lowered tilt by tail suspension. In 1.5G countermeasure group, on the base of suspension, rats were treated with inertial centrifugal force in 1 h/d by rotary system and the acceleration of
back-breast direction is 1.5G in the countermeasure group. The rats were slaughtered at 21 d; alveolar samples containing teeth were routinely prepared.
Three experiments were carried out as following:
1. Morphological changes of dentin, dental pulp and periodontium of simulated weightlessness rats.
Specimens were prepared normally, stained using HE and improved Mallory's method. The following conclusions are:
1.1 In suspension group, dental pulp appeared apparent congestion, edema and leukocyte effusion., this might be related with dental pulp's special anatomical structures.
1.2 In dental pulp, light congestion and dropsy appeared, which suggested that the effect of countermeasure was not enough to eliminate pathological changes of dental pulp.
1.3 Simulated weightlessness had little influence on periodontium and alveolar bone. This might due to their adequate blood supply and strong compensating potential.
1.4 Abnormal mineralization of halfway dentin near dental pulp in suspension group could be observed, which implied that pulp tissues were influenced by weightlessness and resulted in the prohibiting of dentin mineralization
1.5 Artificial countermeasure can only partially improve dentin-mineralized level in part, which was decided by pulp condition. 2. Metabolic changes of Ca, P, Zn in dentin,dental pulp and periodontium of simulated weightlessness rats.
Ca concentration was an important mineralized symbol of dentin
and alveolar bone. P and Zn were closely related with ALP. P was also an important element consisting of hydroxyphosphate crystal and organic materials. The relative percentage of Ca, P, Zn in the dentin, dental pulp and alveolar bone of rats in three groups were analyzed using energy spectrum analysis, to investigate the metabolism of Ca. P, Zn in dentin,pulp,alveolar bones of simulated weightlessness rats, and the protective effect of 1.5G countermeasure.
Results were found as follows:
2.1 The Ca, P, Zn concentration of dentin altered due to weightlessness in simulated weightlessness rats respectively, and the relative percentage of Ca declined significantly. P increased slightly, no apparent changes of Zn were found. It was implied that weightlessness might bring about deformed mineralization.
2.2. The energy spectrum analysis was not fit for the analysis of Ca, P, Zn concentration alteration in dental pulp and alveolar.
2.3 There were no significant differences among three groups about Ca, P, Zn concentration of alveolar bone. It was suggested tha
引文
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33． AllistonT,Choyl,Ducy P et al. TGF-beta-induced repression of CBFAL by Smad3 decreases cbfal and osteocalcin expression and inhibits osteoblast differentiation. EMBO J,2001; 20(9) :2254-2272
34． Raab-Cullen DM, Thiede MA, Peterson DN, et al. Mechanical loading stimulates rapid changes in periosteal gene expression. Calcif Tissue Int. 1994; 55(6) ;473-478
35． Tani-Ishii NAU, Tsunoda AAU, Teranaka TAU, et al. Autocrine regulation of osteoclast formation and bone resorption by 1L-1 alpha and TNF alpha. J Dent Res, 1999; 78(10) :1617-1632
36． Panagakos FS, Fernandez C, Kumar S, et al. Ultrastructural analysis of mineralized matrix form human osteoblastic cells: effects of tumor necrosis factor-alpha. Mol Cell Biochem, 1996; 158(1) :81-89
37． Chapes SK, Morrison DR, Guikema JA, et al. Production and action of cytokines in space. Adv Space Res, 1994; 14(8) :5-19
38． Ong-JL,Bess EG,Bessho-K. Osteoblast progenitor cell response to charaterized titanium surfaces in the presence of bone morphogenetic protein-atelopeptide typel collagen in vitro.J-oral-Implanted, 1999; 25(2) :95-100
39． Bi-LX, Simmons DJ, Mainous. Expression of BMP-2 by rat bone marrow slromal cells in culture. Calcif Tissue Int, 1999; 64(l):63-68
40． Roberts WE. Suppression of osteoblast differentiation during weightlessness. Physiolgist, 1981;24(6) :S75-S76
41． Marie P. Bone morphogenic proteins(BMPs) and bone repair. Rev Chir Orthop Reparatrice Appar Mot,2000,86suppl 1:151-2
42． Chili R, Boyle WJ, Meek J, et al. The c-fos protein interacts with c-Jun/AP-1 to
stimulate transcription of AP-l responsive genes. Cell, 1998; 54:541
43． Legal L, Salle G. Long-lasting and sequential increase of c-fos protein expression in kainic acid-induced status epilepticus. Neurosci Lett, 1998: 88:127-130 44 Morgan JI, Cohon DR, Hempstead JL. Mapping patterns of c-fos expression in the CNS after seisure. Science, 1987;237:192-197
45． 韩济生。神经科学纲要。北京:北京医科大学中国协和医科大学联合出版社,1993;272,281-288 ,l993 ;272,281-288
46． Bading H, Segal MM. N-Methyl-o-Aspartate receptors are critical for mediating the effects of Glutamete on intracellular calcium concentration and immediate early gene expression in cultured hippocampal neurons. Nemo Science, 1995,; 64(3) :653-654
47． Kumei Y ,Akiyam H, Hirano M, et al. Space flight modulates signal transduction pathway of growth factor receptors in rat osteoblasts. Biol Sci Space, 1999;13(3) :142-143
48． Akiyama H , Kanai S ; Hirano M ; et al. Expression of PDGF-beta receptor. EGF receptor, and receptor adapter protein Shc in rat osteoblasts during spaceflight. Mol Cell Biochem, 1999; 202(1-2) :63-71
49． sato A , Hamazaki T, Ocmura T, et al. Effects of microgravity on c-fos gene expression in osteoblast-like Mc3T3-El cells. Adv Space Res, 1999; 24(6) :807-813
50 . Boonstra J. Growth factor-induced signal transduction in adherent mammalian cells is sensitive to gravity. Fas EB J. 1999;13(Suppl):S35-S42
51． Hughes-Ful ford M, Tjandrawinata R , Fitzgerald J , et al. Effects of microgravity on osteoblast growth. Gravit Space Biol Bull, 1998; 11(2) :51-56
52． Matsumoto T, Nakayama K, Kodama Y, et al. Effects of mechanical loading
and reloading on periosteal bone formation and gene expression in tail-suspended rapidly growing rats. Bone, 1998; 22(5Suppl):S89-S93
53． Prokhonchukov AA , Komissarova NA , Zhizhina NA , et al . Comparative study of the effect of weightless and artificial gravity on the density ash, calcium, and phosphorous content of calcified tissue. Kosm Biol Aviakosm Med, 1980;14(4) :23-26
54． Colleran PN , Wilkerson MK , Bloomfield SA, et al. Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling. J Appl Physiol, 2000;89(3) : 1046-1054
55． Yamaguchi M , Ozaki K, Hoshi T, el al. Simulated weightlessness and bone cell function: effect of bone-stimulating factors. In: Yajimak, ed. Aerospace science. Tokyo: Nihon University, 1989;409-415
56． Ouyang H, Mccauley LK, Berry JE, et al. Response of immortalized murine cementoblasts/periodontal ligament cells to parathyroid hormone and parathyroid hormone-related protein in vitro. Arch Oral Biol, 2000;45(4) :293-303
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60． Savostin-Asling L , Asling CW. Mineralization in teeth and jaws , as judged radiographically in rats of the Cosmos-782 experiment. In: Rosenzweig SN, eds. Final reports of U.S. experiments flown on the Soviet satellite Cosmos 782． Washington DC, NASA Heasquarters,1978; 308-320． [NASA technical memorandum]
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66． Fielder PJ , Morey ER, Roberts WETI. Osteoblast histogenesis in periodontal ligament and tibial metaphysics during simulated weightlessness. Aviat Space Environ Med. 1986; 57(12Ptl):l 125-1130
67． Rosenberg GD , Campbell SC , Simmons DJ . The effects of spaceflight on the mineralization of rat incisor dentin. Proc Soc Exp. Biol Med, 1984; 175(4) :429-437
68． Simmons DJ , Russell JE , Winter F, et al . Effects of spaceflight on the non-weight-bearing bones of rat skeleton. Am J Physiol, 1983;244(3) : R319-326
69． Carlson OG , Zackrission K , Marginal alveolar bone loss in flying personnel: a radiographical following study. Aviat Space Environ Med, 1977;48(9) :805-807
70． Pokhonchukov AA, Tigranian RA, Kolesnik AG, et al. Calcium and phosphorus content and teeth of rats after a 22-day orbital space flight on board the Cosmos-605 satellite ship. Koam Biol Aviakosm Med. 1997; 11(1 ):26-30
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22. Garetto LP, Gonzales MR, Morey ER, et al. Preosteoblast production 55 hours after a 12.5 day space flight on Kosmos-1887. FASEBJ, 1990;4(1):24～48
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26. Westerlind KC, Turner RT. The skeletal effects of spaceflight in growing rats: tissue-specific alterations in mRNA levels for TGF-beta. J Bone Miner Res, 1995; 10(6): 843～848
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31. Erlebacher A, Filvaroff EH, Ye JQ, et al. Osteoblastic response to TGF-beta during bone remodeling. Mol Biol Cell, 1998; 9(7):1903～1918
32. Zhang R, Supowit SC, Hou X, et al. Transforming growth factor-beta2
mRNA levei in unloaded bone analyzed by quantitative in situ hybridization. Calcif Tissue Int, 1999; 64(6) :522-526
33． AllistonT,Choyl,Ducy P et al. TGF-beta-induced repression of CBFAL by Smad3 decreases cbfal and osteocalcin expression and inhibits osteoblast differentiation. EMBO J,2001; 20(9) :2254-2272
34． Raab-Cullen DM, Thiede MA, Peterson DN, et al. Mechanical loading stimulates rapid changes in periosteal gene expression. Calcif Tissue Int. 1994; 55(6) ;473-478
35． Tani-Ishii NAU, Tsunoda AAU, Teranaka TAU, et al. Autocrine regulation of osteoclast formation and bone resorption by 1L-1 alpha and TNF alpha. J Dent Res, 1999; 78(10) :1617-1632
36． Panagakos FS, Fernandez C, Kumar S, et al. Ultrastructural analysis of mineralized matrix form human osteoblastic cells: effects of tumor necrosis factor-alpha. Mol Cell Biochem, 1996; 158(1) :81-89
37． Chapes SK, Morrison DR, Guikema JA, et al. Production and action of cytokines in space. Adv Space Res, 1994; 14(8) :5-19
38． Ong-JL,Bess EG,Bessho-K. Osteoblast progenitor cell response to charaterized titanium surfaces in the presence of bone morphogenetic protein-atelopeptide typel collagen in vitro.J-oral-Implanted, 1999; 25(2) :95-100
39． Bi-LX, Simmons DJ, Mainous. Expression of BMP-2 by rat bone marrow slromal cells in culture. Calcif Tissue Int, 1999; 64(l):63-68
40． Roberts WE. Suppression of osteoblast differentiation during weightlessness. Physiolgist, 1981;24(6) :S75-S76
41． Marie P. Bone morphogenic proteins(BMPs) and bone repair. Rev Chir Orthop Reparatrice Appar Mot,2000,86suppl 1:151-2
42． Chili R, Boyle WJ, Meek J, et al. The c-fos protein interacts with c-Jun/AP-1 to
stimulate transcription of AP-l responsive genes. Cell, 1998; 54:541
43． Legal L, Salle G. Long-lasting and sequential increase of c-fos protein expression in kainic acid-induced status epilepticus. Neurosci Lett, 1998: 88:127-130 44 Morgan JI, Cohon DR, Hempstead JL. Mapping patterns of c-fos expression in the CNS after seisure. Science, 1987;237:192-197
45． 韩济生。神经科学纲要。北京:北京医科大学中国协和医科大学联合出版社,1993;272,281-288 ,l993 ;272,281-288
46． Bading H, Segal MM. N-Methyl-o-Aspartate receptors are critical for mediating the effects of Glutamete on intracellular calcium concentration and immediate early gene expression in cultured hippocampal neurons. Nemo Science, 1995,; 64(3) :653-654
47． Kumei Y ,Akiyam H, Hirano M, et al. Space flight modulates signal transduction pathway of growth factor receptors in rat osteoblasts. Biol Sci Space, 1999;13(3) :142-143
48． Akiyama H , Kanai S ; Hirano M ; et al. Expression of PDGF-beta receptor. EGF receptor, and receptor adapter protein Shc in rat osteoblasts during spaceflight. Mol Cell Biochem, 1999; 202(1-2) :63-71
49． sato A , Hamazaki T, Ocmura T, et al. Effects of microgravity on c-fos gene expression in osteoblast-like Mc3T3-El cells. Adv Space Res, 1999; 24(6) :807-813
50 . Boonstra J. Growth factor-induced signal transduction in adherent mammalian cells is sensitive to gravity. Fas EB J. 1999;13(Suppl):S35-S42
51． Hughes-Ful ford M, Tjandrawinata R , Fitzgerald J , et al. Effects of microgravity on osteoblast growth. Gravit Space Biol Bull, 1998; 11(2) :51-56
52． Matsumoto T, Nakayama K, Kodama Y, et al. Effects of mechanical loading
and reloading on periosteal bone formation and gene expression in tail-suspended rapidly growing rats. Bone, 1998; 22(5Suppl):S89-S93
53． Prokhonchukov AA , Komissarova NA , Zhizhina NA , et al . Comparative study of the effect of weightless and artificial gravity on the density ash, calcium, and phosphorous content of calcified tissue. Kosm Biol Aviakosm Med, 1980;14(4) :23-26
54． Colleran PN , Wilkerson MK , Bloomfield SA, et al. Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling. J Appl Physiol, 2000;89(3) : 1046-1054
55． Yamaguchi M , Ozaki K, Hoshi T, el al. Simulated weightlessness and bone cell function: effect of bone-stimulating factors. In: Yajimak, ed. Aerospace science. Tokyo: Nihon University, 1989;409-415
56． Ouyang H, Mccauley LK, Berry JE, et al. Response of immortalized murine cementoblasts/periodontal ligament cells to parathyroid hormone and parathyroid hormone-related protein in vitro. Arch Oral Biol, 2000;45(4) :293-303
57． Garetto LP , Roberts WE , Gonsalves MR. Experiment k-6-03． Gravity and skeletal growth. Part Ⅲ : nuclear volume analysis of osteoblasl histogenesis in periodontal ligament cells of cosmos-1887 rats. In: connolly JP, Grindeland RE, Ballard RW, eds. Final reports of the U.S experiments flown on the Soviet biosatellite Cosmos 1887． Washington DC, NASA Headquarters, 1990; 139-146[NASA technical memorandum]
58． Garetto LP , Morey-Holton ER , Roberts, et al. Preliminary analysis of rat periodontal ligament osteoblast histogenesis from SLS-1． ASGSB Bull, 1992: 6(1) :58
59． Simons DJ, Grynpas MD , Rosenberg GD, et al. Maturation of bone and dentin
matrices in rats flown on the Soviet Cosmos 1887． FASEB J,1990;4(l):29-33
60． Savostin-Asling L , Asling CW. Mineralization in teeth and jaws , as judged radiographically in rats of the Cosmos-782 experiment. In: Rosenzweig SN, eds. Final reports of U.S. experiments flown on the Soviet satellite Cosmos 782． Washington DC, NASA Heasquarters,1978; 308-320． [NASA technical memorandum]
61． Simons DJ , Russell JE , Winter F. Et al. The effect of spaceflight on osteogenesis and dentinogenesis in the mandible of rats. [In: Heinrich MR, Sonza KA, eds. Final reports of US rat experiments flown on the Soviet satellite Cosmos 1129． Washington DC, NASA Heasquarters,1981; 270-306． [NASA technical memorandum]
62． Tranvan P , Vignery A , Baron R. The effect of space flight on osteogenesis and dentiongenesis in the mandible of rats. Supplement I: the effect of space flight on alveolar bone modeling and remodeling in the rat mandible. [In: Heinrich MR, Sonza KA, eds. Final reports of U.S. rat experiments flown on the Soviet satellite Cosmos 1129． Washington DC, NASA Heasquarters,1981; 307-324． [NASA technical memorandum]
63． Roberts WE, Mozsary PG, Horey-Holton E. Quantitative analysis of selected bone parameters. Supplemental report I: effects of weightlessness on osteoblast differentiation in rat molar periodontium. [In: Heinrich MR, Sonza KA, eds. Final reports of US rat experiments flown on the Soviet satellite Cosmos 1129． Washington DC, NASA Heasquarters,1981; 127-148． [NASA technical memorandum]
64． Doty S . Effects of microgravity on rat bone , cartilage and connective tissues. [In: Heinrich MR, Sonza KA, eds. Final reports of US rat experiments flown on the Soviet satellite Cosmos 1129． Washington DC, NASA
Heasquarters, 1981; 51-56． [NASA technical memorandum]
65． Kleber BM , Weigt D , Weingart H, et al. Structural changes in the dental hard substances and jaw bones of animals due to short-duration weiglltlessness. Zabn, Mund Kieferheilk. Zentraibl. 1989;77(7) :668-673
66． Fielder PJ , Morey ER, Roberts WETI. Osteoblast histogenesis in periodontal ligament and tibial metaphysics during simulated weightlessness. Aviat Space Environ Med. 1986; 57(12Ptl):l 125-1130
67． Rosenberg GD , Campbell SC , Simmons DJ . The effects of spaceflight on the mineralization of rat incisor dentin. Proc Soc Exp. Biol Med, 1984; 175(4) :429-437
68． Simmons DJ , Russell JE , Winter F, et al . Effects of spaceflight on the non-weight-bearing bones of rat skeleton. Am J Physiol, 1983;244(3) : R319-326
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