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甲状旁腺激素促成骨作用的初步研究

Primary Study on the Anabolic Effects of Parathyroid Hormone in Vivo

【作者】 吕国良

【导师】 张克勤;

【作者基本信息】 南京医科大学 , 内科学, 2004, 硕士

【摘要】 目的 探讨卵巢切除及间歇注射人甲状旁腺激素1-34片段对大鼠局部骨组织中胰岛素样生长因子1(IGF-1)表达的影响,同时检测血清中转化生长因子β1(TGF-β1)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)表达变化,从而评价各种细胞因子在绝经后骨质疏松的发病及PTH促成骨机理中的作用。 方法 3月龄雌性SD大鼠随机分为3组:假手术组(Sham)、去卵巢对照组(OVX)、去卵巢PTH注射组(PTH),每组6只。假手术组暴露双侧卵巢并切除一块与卵巢大小相同的脂肪组织,去卵巢对照组和去卵巢PTH注射组于卵巢切除两周后分别皮下注射PBS溶剂或hPTH1-34,6ug/100g体重,10天后所有大鼠一批处死,腹主动脉取血分离血清,-20℃保存。取胫骨中上1/3制备脱钙骨标本,免疫组化法(IHC)检测骨组织中细胞因子IGF-1的蛋白表达;酶联免疫吸附法(ELISA)检测血清中细胞因子TGF-β、IL-6、IL-1β、TNF-α的含量。 结果 成骨细胞呈线状排列于骨小梁的边缘,细胞因子IGF-1表达于成骨细胞胞浆,骨细胞、软骨细胞及骨基质中也存在IGF-1。不同部位的成骨细胞IGF-1的表达量并不一致,卵巢切除及PTH注射对不同部位成骨细胞IGF-1表达的影响也不一样。卵巢切除后软骨细胞 南京医科大学硕士学位论文工GF一1表达降低,皮质骨及小梁骨部位成骨细胞的工GF一1表达无明显变化。PTH注射对软骨区及皮质骨区IGF一表达无显著影响,但可以明显增加小梁骨部位成骨细胞IGF一1的表达。萝尸巢切除后血清中细胞因子TGF一日:升高,但去卵巢PTH注射组与去卵巢对照组无显著差异。大鼠血清中IL一1日、工L6、TNF一a含量较低,各组间未见显著差异。 结论局部骨中细胞因子IGF一1在PTH的促成骨机理中起着重要作用;间隙性PTH注射对血液循环中TGF一日,、IL一6、IL一1日、TNF-a无明显影响,其在局部骨组织中的变化尚有待于进一步研究。

【Abstract】 Objective: To evaluate the effects of ovariectomy and intermittent injection of human parathyroid hormone(1-34) on the protein level of local insulin-like growth factor-1 (IGF-1) , Meanwhile transforming growth factor- P 1 (TGF- P 1), interlukin-6(IL-6), interlukin-1 P (IL-1 P ), tumor necrosis factor- a (TNF- a ) in serum were detected.Methods: Three month-old rats were ovariectomied(OVX) or sham-operated (SHAM). Two weeks after operation, OVX rats received daily subcutaneous injection of human parathyroid hormone fragment 1-34 (hPTH 1-34), 6ug/100g body weight or vehicle for 10 days. Then all animals were sacrificed. The tibiae of the rats were kept for the samples of decalcification, IGF-1 in bone tissue was measured by immunohistochemistry and Enzyme linked-immuno-sorbent assay (ELISA) was used to detect the TGF- P 1, IL-6, IL-1 P and TNF- a in serum.Results: IGF-1 locates in the cytoplasts of osteoblasts, OVX has no effects on the protein level of IGF-1 in rat bone tissue and injection of hPTH (1-34) can increase its expression in cancellous , However nodifference of TGF- β1 level was found in OVX rats treated with or without hPTH (1-34) . The concentrations of IL-1 β, IL-6, TNF- are lower and no difference were found in three groups.Conclusion: Our findings suggest that IGF-1 in local bone tissue plays an important role in the anabolic effects of PTH and intermittent injection of PTH has no effects on the concentration of TGF- β1 , IL-6, IL-1 β , TNF- in serum.

  • 【分类号】R58
  • 【下载频次】132
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