HIF-1信号通路与绝经后骨质疏松的关系研究

发布时间：2018-06-06 01:28

  本文选题：去卵巢 + 骨质疏松　； 参考：《四川大学学报(医学版)》2017年06期

【摘要】：目的初步探索低氧诱导因子-1(HIF-1)信号通路在绝经后骨质疏松(PMOP)发病过程中的作用及其作用机制。方法 C57BL/6J雌性小鼠随机分为假手术组(A组)、去卵巢绝经后骨质疏松组(B组)、溶剂对照组(C组)和HIF-1α抑制剂2-甲氧雌二醇(2ME2)治疗组(D组),每组15只。造模后3月处死小鼠,采用ELISA检测血清雌激素、小鼠Ⅰ型前胶原氨基末端肽(PINP)及小鼠Ⅰ型胶原羧基末端肽(CTX-1)等骨代谢指标,HE染色和抗酒石酸酸性磷酸酶(TRAP)染色观察骨结构及破骨细胞变化,免疫组化检测HIF-1α、HIF-1β、脯氨酰羟化酶结构域蛋白(PHD)、Hipple-Lindau肿瘤抑制蛋白(VHL)及低氧诱导因子抑制因子(FIH)等HIF-1信号通路的调节产物。取A、B组小鼠骨髓诱导培养破骨细胞,Western blot检测抑制蛋白激酶B(Akt)、细胞外调节蛋白激酶(ERK)、核因子-κB(NF-κB)信号通路后破骨细胞内HIF-1α变化。结果 B组小鼠骨代谢指标较A组升高(P0.001),破骨细胞HIF-1α蛋白阳性表达,骨髓区HIF-1α蛋白表达量较A组升高(P0.001),HIF-1β、PHD、VHL、FIH水平无明显变化。HIF-1α抑制剂抑制HIF-1后,去卵巢骨质疏松小鼠骨代谢指标降低(P0.001),骨质疏松程度明显改善。予以Akt、ERK、NF-κB信号通路抑制剂干预后,去卵巢骨质疏松小鼠破骨细胞内HIF-1α水平均下降(P0.05)。结论 HIF-1信号通路参与了小鼠PMOP的病理演变过程,抑制HIF-1信号通路可改善PMOP的严重程度;PMOP破骨细胞内HIF-1信号通路的上调可能与Akt、ERK、NF-κB这3条信号通路有关。
[Abstract]:Objective to explore the role and mechanism of hypoxia inducible factor-1 (HIF-1) signaling pathway in postmenopausal osteoporosis (PMOP). Methods C57BL/6J female mice were randomly divided into three groups: sham operation group (group A), ovariectomized osteoporosis group (group B) and solvent control group (group C) and group D treated with HIF-1 伪 inhibitor 2-methoxyestradiol (2ME2) with 15 rats in each group. Three months after the model, mice were killed and serum estrogen was detected by ELISA. The changes of bone structure and osteoclasts were observed by HE staining and tartrate-resistant acid phosphatase (TRAPP) staining, such as mouse procollagen amino-terminal peptide (PINP) and mouse type 鈪，

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