本文選題：去卵巢 + 骨質(zhì)疏松　； 參考：《四川大學(xué)學(xué)報(醫(yī)學(xué)版)》2017年06期

【摘要】：目的初步探索低氧誘導(dǎo)因子-1(HIF-1)信號通路在絕經(jīng)后骨質(zhì)疏松(PMOP)發(fā)病過程中的作用及其作用機(jī)制。方法 C57BL/6J雌性小鼠隨機(jī)分為假手術(shù)組(A組)、去卵巢絕經(jīng)后骨質(zhì)疏松組(B組)、溶劑對照組(C組)和HIF-1α抑制劑2-甲氧雌二醇(2ME2)治療組(D組),每組15只。造模后3月處死小鼠,采用ELISA檢測血清雌激素、小鼠Ⅰ型前膠原氨基末端肽(PINP)及小鼠Ⅰ型膠原羧基末端肽(CTX-1)等骨代謝指標(biāo),HE染色和抗酒石酸酸性磷酸酶(TRAP)染色觀察骨結(jié)構(gòu)及破骨細(xì)胞變化,免疫組化檢測HIF-1α、HIF-1β、脯氨酰羥化酶結(jié)構(gòu)域蛋白(PHD)、Hipple-Lindau腫瘤抑制蛋白(VHL)及低氧誘導(dǎo)因子抑制因子(FIH)等HIF-1信號通路的調(diào)節(jié)產(chǎn)物。取A、B組小鼠骨髓誘導(dǎo)培養(yǎng)破骨細(xì)胞,Western blot檢測抑制蛋白激酶B(Akt)、細(xì)胞外調(diào)節(jié)蛋白激酶(ERK)、核因子-κB(NF-κB)信號通路后破骨細(xì)胞內(nèi)HIF-1α變化。結(jié)果 B組小鼠骨代謝指標(biāo)較A組升高(P0.001),破骨細(xì)胞HIF-1α蛋白陽性表達(dá),骨髓區(qū)HIF-1α蛋白表達(dá)量較A組升高(P0.001),HIF-1β、PHD、VHL、FIH水平無明顯變化。HIF-1α抑制劑抑制HIF-1后,去卵巢骨質(zhì)疏松小鼠骨代謝指標(biāo)降低(P0.001),骨質(zhì)疏松程度明顯改善。予以Akt、ERK、NF-κB信號通路抑制劑干預(yù)后,去卵巢骨質(zhì)疏松小鼠破骨細(xì)胞內(nèi)HIF-1α水平均下降(P0.05)。結(jié)論 HIF-1信號通路參與了小鼠PMOP的病理演變過程,抑制HIF-1信號通路可改善PMOP的嚴(yán)重程度;PMOP破骨細(xì)胞內(nèi)HIF-1信號通路的上調(diào)可能與Akt、ERK、NF-κB這3條信號通路有關(guān)。
[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 偽 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，

本文編號：1984374