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熱休克蛋白70對(duì)新生大鼠缺氧性肺動(dòng)脈高壓的保護(hù)作用

發(fā)布時(shí)間:2018-03-01 14:30

  本文關(guān)鍵詞: 熱休克蛋白 缺氧誘導(dǎo)因子-α 缺氧性肺動(dòng)脈高壓 新生大鼠 出處:《中國(guó)當(dāng)代兒科雜志》2017年01期  論文類(lèi)型:期刊論文


【摘要】:目的 探討熱休克蛋白70(HSP70)在新生大鼠缺氧性肺動(dòng)脈高壓(HPH)中的保護(hù)作用。方法 將128只新生大鼠隨機(jī)分為空白對(duì)照組、HPH模型組、空病毒對(duì)照組和HSP70組(n=32)。建立HPH模型前分別向空白對(duì)照組和HPH模型組大鼠通過(guò)尾靜脈注射5μL無(wú)菌鹽水,向空病毒對(duì)照組大鼠通過(guò)尾靜脈注射5μL Ad-GFP(1 010 PFU/m L),向HSP70組大鼠通過(guò)尾靜脈注射5μL Ad-HSP70(1 010 PFU/m L),轉(zhuǎn)染后除空白對(duì)照組外,其余3組建立HPH模型。分別于建模后3、7、10、14 d,采用多導(dǎo)生理記錄儀記錄各組平均肺動(dòng)脈壓力(m PAP),光學(xué)及電子顯微鏡觀(guān)察肺血管組織結(jié)構(gòu)及重塑指標(biāo),Western blot法檢測(cè)各組新生大鼠肺組織中HSP70、缺氧誘導(dǎo)因子-1α(HIF-1α)、縮血管因子內(nèi)皮素-1(ET-1)、誘導(dǎo)型一氧化氮合酶(i NOS)蛋白表達(dá)水平。結(jié)果 HPH模型組與空病毒對(duì)照組在3、7、10、14 d時(shí)的m PAP水平高于空白對(duì)照組(P0.05)。缺氧7、10 d時(shí),空白對(duì)照組及HSP70組MA%、MT%低于HPH模型組和空病毒對(duì)照組(P0.01);缺氧14 d時(shí),HPH模型組、空病毒對(duì)照組和HSP70組MA%、MT%比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),但高于空白對(duì)照組(P0.01)。缺氧3、7、10 d時(shí),HSP70組HSP70的蛋白表達(dá)水平高于HPH模型組、空病毒對(duì)照組和空白對(duì)照組(P0.01);HSP70組HIF-1α、ET-1和i NOS表達(dá)水平低于HPH模型組和空病毒對(duì)照組(P0.05),而與空白對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論 轉(zhuǎn)染HSP70可以提高HPH新生大鼠肺組織HSP70表達(dá),下調(diào)HIF-1α、ET-1、i NOS表達(dá),減輕肺血管重塑,降低肺動(dòng)脈壓力,可能成為治療新生兒HPH的一種新策略。
[Abstract]:Objective to investigate the protective effect of heat shock protein 70 (HSP70) on hypoxic pulmonary hypertension (HPH) in neonatal rats. Before the establishment of HPH model, rats in blank control group and HPH model group were injected with 5 渭 L aseptic saline through tail vein, respectively. Rats in the empty virus group were injected with 5 渭 L Ad-GFP(1 010 PFU/m L Ad-GFP(1 through tail vein, and 5 渭 L Ad-HSP70(1 010 PFU/m L with 5 渭 L Ad-HSP70(1 010 PFU/m L in HSP70 group. After transfection, 5 渭 L Ad-HSP70(1 010 PFU/m L was injected into the control group except the blank control group. The HPH model was established in the other three groups, and the mean pulmonary artery pressure was recorded by multichannel physiological recorder on the 14th day after modeling. The tissue structure and remodeling index of pulmonary vessels were observed by optical and electron microscopy. The expression levels of HSP70, HIF-1 偽, endothelin-1, inducible nitric oxide synthase (iNOS) protein in lung tissue of newborn rats were higher than those in control group at day 14. Results the level of m PAP in HPH model group and empty virus control group was higher than that in blank control group at day 14. In the exposure group, P0.05, 10 days after hypoxia, The percentage of MT% in the blank control group and HSP70 group was lower than that in the HPH model group and the empty virus control group (P0.01). There was no significant difference in MT% between the control group and the HSP70 group, but it was higher than that in the blank control group (P 0.01). The expression of HSP70 protein in the HSP70 group was higher than that in the HPH model group at 10 days after hypoxia. The expression levels of HIF-1 偽 -ET-1 and I NOS in the empty virus control group and the blank control group were lower than those in the HPH model group and the empty virus control group, but there was no significant difference compared with the blank control group. Conclusion transfection of HSP70 can increase the expression of HSP70 in the lung tissue of the neonatal HPH rats. Down-regulating the expression of HIF-1 偽 -ET-1 NOS, reducing pulmonary vascular remodeling and reducing pulmonary artery pressure may be a new strategy for the treatment of neonatal HPH.
【作者單位】: 新疆醫(yī)科大學(xué)第一附屬醫(yī)院新生兒科;新疆伊犁州奎屯醫(yī)院兒科;

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