發(fā)布時(shí)間：2018-05-09 00:10

  本文選題：維生素A + 鐵代謝　； 參考：《重慶醫(yī)科大學(xué)》2009年博士論文

【摘要】： 第一部分人群維生素A營(yíng)養(yǎng)狀況與鐵代謝穩(wěn)態(tài)相關(guān)性研究 目的:橫斷面調(diào)查學(xué)齡前兒童維生素A營(yíng)養(yǎng)狀況與鐵代謝動(dòng)態(tài)平衡及機(jī)體總鐵含量之間的關(guān)系,并評(píng)估不同維生素A營(yíng)養(yǎng)狀況下貧血與儲(chǔ)鐵不足的患病風(fēng)險(xiǎn)。 方法:利用整群抽樣和分層抽樣相結(jié)合的方法從巴南區(qū)魚(yú)洞鎮(zhèn)共20多所幼兒園隨機(jī)抽取其中4所進(jìn)行調(diào)查,同時(shí)問(wèn)卷調(diào)查其人口學(xué)資料、社會(huì)經(jīng)濟(jì)狀況以及飲食習(xí)慣等。利用高效液相色譜法測(cè)定血清維生素A濃度,酶聯(lián)免疫法測(cè)定血清鐵蛋白(serum ferritin, SF)水平、微粒子增強(qiáng)透射免疫法檢測(cè)可溶性轉(zhuǎn)鐵蛋白受體(serum transferrin receptor, sTfR)水平、透射免疫比濁法測(cè)定血清C-反應(yīng)蛋白(C- reactive protein, CRP)水平以及高鐵氰化法測(cè)定血紅蛋白(hemoglobin, HB)濃度,并計(jì)算sTfR-SF指數(shù)(TFR-F指數(shù))以及機(jī)體總鐵含量。 結(jié)果:共471名學(xué)齡前兒童納入研究,其中男童236名,女童235名,年齡范圍為2～7歲,平均年齡為(4.0±0.85)(均數(shù)±標(biāo)準(zhǔn)差)歲。HB水平為(115.8±9.2)g/L ,貧血患病率為23.5 %; SF水平為(24.75±14.71)μg/L,sTfR水平為(1.28±0.33)mg/L,儲(chǔ)鐵不足發(fā)生率為45.1%。血清維生素A水平為(1.21±0.36)μmol/L,維生素A缺乏(vitamin A deficiency, VAD)患病率為6.5%,可疑亞臨床維生素A缺乏( suspect sub-clinic vitamin A deficiency, SSVAD)患病率為26.0%。TFR-F指數(shù)0.9595 (0.7257,1.2226)[中位數(shù)(P25,P75)] ,機(jī)體鐵含量8.868 (6.986,10.470) mg/kg。校正兒童年齡、性別、不同幼兒園來(lái)源、家庭經(jīng)濟(jì)狀況以及膳食模式等因素后,血清維生素A與HB、SF對(duì)數(shù)濃度、sTfR水平、TFR-F指數(shù)以及機(jī)體鐵含量的偏相關(guān)系數(shù)(radjust)分別是0.16(p0.001), -0.13 (p=0.037), 0.17 (p=0.0011), -0.013 (p=0.7935)以及-0.05 (p=0.3652)。Logitic回歸分析顯示,VAD是導(dǎo)致儲(chǔ)鐵不足(以SF水平作為判斷標(biāo)準(zhǔn))的獨(dú)立危險(xiǎn)因素[優(yōu)勢(shì)比(odds ratio, OR)(95% CI): 1.88(1.01, 2.97)。若以TFR-F為判斷指標(biāo),VAD則不是儲(chǔ)鐵不足患病危險(xiǎn)因素[OR(95% CI): 1.365(0.286,6.513)]。VAD兒童患貧血的危險(xiǎn)性[OR (95% CI): 2.56(1.15,5.70)]是NVA兒童貧血患病風(fēng)險(xiǎn)的2.56倍;若對(duì)SF和sTfR校正以后,VAD兒童貧血患病風(fēng)險(xiǎn)則明顯下降[OR (95% CI): 1.53(1.01,1.88)]。 結(jié)論: 1學(xué)齡前兒童血清維生素A水平與反映機(jī)體鐵儲(chǔ)備和鐵利用的生化指標(biāo)密切相關(guān),而與鐵吸收及機(jī)體總鐵含量無(wú)明顯關(guān)系。 2 VAD是儲(chǔ)鐵不足患病的獨(dú)立危險(xiǎn)因素,其可能主要通過(guò)影響鐵儲(chǔ)備和鐵利用產(chǎn)生作用,而對(duì)鐵吸收影響不大。 3 VAD是貧血患病的獨(dú)立危險(xiǎn)因素,除主要影響鐵代謝外,還可能通過(guò)其他途徑產(chǎn)生作用。 第二部分維生素A等多種微量營(yíng)養(yǎng)素干預(yù)對(duì)鐵代謝穩(wěn)態(tài)的影響 目的:觀察單獨(dú)維生素A補(bǔ)充、維生素A+鐵以及多種微量營(yíng)養(yǎng)素聯(lián)合補(bǔ)充等干預(yù)方式對(duì)鐵代謝相關(guān)生化指標(biāo)的影響,并評(píng)估不同干預(yù)方式對(duì)貧血以及儲(chǔ)鐵不足發(fā)病的保護(hù)作用。 方法:本研究為隨機(jī)、對(duì)照、盲法現(xiàn)場(chǎng)干預(yù)試驗(yàn),對(duì)象來(lái)源于第一部分研究。從該地區(qū)共20多所幼兒園中隨機(jī)選取3所中的全部226名2-7歲學(xué)齡前兒童納入計(jì)劃干預(yù)對(duì)象。對(duì)其分別補(bǔ)充100%RDA的維生素A(Ⅰ組),維生素A加鐵(Ⅱ組)以及維生素A,鐵,維生素B1,核黃素,葉酸,尼克酸,鋅以及鈣(Ⅲ組)。干預(yù)前后分別測(cè)定利用高效液相色譜法測(cè)定血清維生素A濃度,酶聯(lián)免疫法測(cè)定血清鐵蛋白(serum ferritin, SF)水平、微粒子增強(qiáng)透射免疫法檢測(cè)可溶性轉(zhuǎn)鐵蛋白受體(serum transferring receptor, sTfR)水平、透射免疫比濁法測(cè)定血清C-反應(yīng)蛋白(C- reactive protein, CRP)水平以及高鐵氰化法測(cè)定血紅蛋白(hemoglobin, HB)濃度,并計(jì)算sTfR-SF指數(shù)(TFR-F指數(shù))及機(jī)體總鐵含量。同時(shí)利用問(wèn)卷方式調(diào)查這些兒童的人口學(xué)治療、社會(huì)經(jīng)濟(jì)狀況以及飲食習(xí)慣等。 結(jié)果:三種干預(yù)方式均可使HB水平均較干預(yù)前明顯升高(P0.0001),但各干預(yù)組間無(wú)顯著差異(p0.05)。干預(yù)后各組維生素A水平均有所提高,而以維生素A+鐵組以及多種微量營(yíng)養(yǎng)素補(bǔ)充組最為明顯(p0.05)。干預(yù)后各組SF值均較干預(yù)前明顯下降(P0.01),而維生素A+鐵補(bǔ)充組以及多種微量營(yíng)養(yǎng)素補(bǔ)充組下降最為明顯(P0.05)。干預(yù)后各組sTfR水平均出現(xiàn)明顯降低(P0.01),尤以單獨(dú)維生素A補(bǔ)充組最明顯(P0.05)。單獨(dú)維生素A補(bǔ)充組其TFR-F指數(shù)以及機(jī)體總鐵含量于干預(yù)前后并無(wú)明顯變化(P0.05)。在校正了兒童性別、年齡、被動(dòng)吸煙、社會(huì)經(jīng)濟(jì)狀況以及膳食模式以后,三種干預(yù)方式對(duì)貧血發(fā)病的保護(hù)作用并無(wú)明顯差異(P0.05)。若以鐵蛋白作為儲(chǔ)鐵不足乏判斷的指標(biāo),三種干預(yù)方式對(duì)儲(chǔ)鐵不足保護(hù)作用也無(wú)差異(P0.05);但若以TFR-F指數(shù)作為判定指標(biāo),則相對(duì)于單獨(dú)維生素A補(bǔ)充而言,維生素A+鐵以及多種微量營(yíng)養(yǎng)素的聯(lián)合補(bǔ)充是儲(chǔ)鐵不足更好的保護(hù)因素[相對(duì)危險(xiǎn)度(relative risk, RR)(95% CI): 0.410(0.218,0.992)]。 結(jié)論: 1維生素A干預(yù)對(duì)鐵儲(chǔ)備及鐵利用過(guò)程均有影響。 2維生素A干預(yù)對(duì)TFR-F指數(shù)以及機(jī)體總鐵含量無(wú)明顯影響,表明維生素A對(duì)鐵在腸道的吸收無(wú)明顯作用。 3維生素A聯(lián)合鐵劑等多種微量營(yíng)養(yǎng)素的補(bǔ)充可能是改善儲(chǔ)鐵不足狀態(tài)的較好干預(yù)方式。 第三部分維生素A營(yíng)養(yǎng)狀況對(duì)鐵調(diào)節(jié)模式的影響及其相關(guān)機(jī)制 目的:了解不同維生素A營(yíng)養(yǎng)狀況下大鼠貧血的性質(zhì)及其對(duì)鐵效應(yīng)元件-鐵調(diào)節(jié)蛋白作用模式(iron responsive element-iron regulated protein, IRE-IRP模式)和肝調(diào)素-膜鐵轉(zhuǎn)運(yùn)蛋白作用模式(hepcidin- ferroportin,Hepc-FPN模式)各組件在肝臟mRNA和蛋白水平表達(dá)的影響。 方法:清潔級(jí)健康雌性Wistar大鼠30只隨機(jī)分為3組,飼以相應(yīng)飼料,3周后與健康雄性Wistar大鼠交配,1:2雌雄合籠::(1)正常維生素A飼喂組母鼠(normal vitamin A status, NVA)(10只),給予維生素A充足飼料(含維生素A 6500 U/kg),隨機(jī)從10窩中每窩各抽取雌雄仔鼠各1只共計(jì)20只用于本實(shí)驗(yàn),仔鼠飼料同母鼠;(2)低維生素A飼喂組母鼠(low vitamin A status, LVA)(10只),給予低維生素A飼料(含維生素A 400IU/kg) ,隨機(jī)從10窩中每窩各抽取雌雄仔鼠各1只共計(jì)20只用于本實(shí)驗(yàn),仔鼠飼料同母鼠,其幼鼠為維生素A缺乏鼠(vitamin A deficiency, VAD);(3)生后4周干預(yù)組母鼠(vitamin A intervention, VAI)(10只),給予低維生素A飼料飼喂至分娩,隨機(jī)從10窩中每窩各抽取雌雄仔鼠各1只共計(jì)20只用于本實(shí)驗(yàn),仔鼠飼料同母鼠,4周齡大小后改飼維生素A充足飼料。各組仔鼠于8周齡處死。用高效液相色譜法(HPLC)檢測(cè)血清維生素A濃度,利用全自動(dòng)血細(xì)胞分析儀測(cè)定全血紅細(xì)胞指數(shù),熒光定量PCR法、Western blotting法以及酶聯(lián)免疫法分別測(cè)定鐵調(diào)節(jié)IRE-IRP模式和Hepc-FPN模式各組件在肝臟mRNA和蛋白水平表達(dá)的水平。 結(jié)果:①仔鼠在第八周時(shí),NVA組和VAD組大鼠外周血紅細(xì)胞計(jì)數(shù)、血紅蛋白濃度以及紅細(xì)胞壓積均無(wú)顯著差異(p0.05),而VAI大鼠上述指標(biāo)均顯著高于前兩組(p0.05)。VAD組紅細(xì)胞平均容積最低(p0.05),NVA組和VAI組大鼠之間則無(wú)顯著差異(p0.05);VAI組大鼠紅細(xì)胞分布寬度顯著高于NVA組和VAD組(p0.05),后兩組該值無(wú)顯著差異(p0.05)。三個(gè)組大鼠平均血紅蛋白含量組間無(wú)差異(p0.05),而VAI組平均血紅蛋白濃度則顯著低于VAN組和MVAD組(p0.05),后兩組該指標(biāo)之間無(wú)顯著差異(p0.05)。②Hepc-FPN模式中肝調(diào)素、骨形成蛋白-4以及白細(xì)胞介素-6在不同維生素A營(yíng)養(yǎng)狀況下其在肝臟的mRNA及蛋白水平的表達(dá)均出現(xiàn)差異。③IRE-IRP模式中鐵調(diào)節(jié)蛋白-1、膜鐵轉(zhuǎn)運(yùn)蛋白-1、鐵蛋白輕鏈以及轉(zhuǎn)鐵蛋白受體-1在不同維生素A營(yíng)養(yǎng)狀況下在肝臟的mRNA及蛋白水平的表達(dá)均出現(xiàn)差異,而二價(jià)金屬離子轉(zhuǎn)運(yùn)體-1的表達(dá)則差異不明顯。 結(jié)論: 1維生素A缺乏時(shí)外周血主要為小細(xì)胞低色素表現(xiàn),補(bǔ)充維生素A可使上述改變有所恢復(fù);維生素A缺乏對(duì)平均血紅蛋白量以及平均血紅蛋白濃度影響不大; 2不同維生素A營(yíng)養(yǎng)狀況對(duì)鐵代謝Hepc-FPN模式具有明顯影響,而其可能途徑是從轉(zhuǎn)錄水平調(diào)節(jié)IL-6和BMP-4生成從而影響Hepcidin的合成的; 3不同維生素A營(yíng)養(yǎng)狀況對(duì)鐵代謝IRE-IRP模式具有明顯影響,而其可能途徑之一是通過(guò)從轉(zhuǎn)錄水平調(diào)節(jié)IRP-1的合成起作用的。
[Abstract]:Study on the relationship between the nutritional status of vitamin A and iron metabolism in the first part of the population



Objective : To investigate the relationship between the nutritional status of vitamin A and the dynamic balance of iron metabolism and the total iron content of iron metabolism in preschool children before school age , and to evaluate the risk of anemia and deficiency of iron in nutritional status of different vitamin A .



Methods : Four of 20 kindergartens were randomly selected from 20 kindergartens in fish - hole town in southern Brazil by cluster sampling and stratified sampling . The levels of serum vitamin A , serum ferritin ( SF ) , serum ferritin ( SF ) and serum C - reactive protein ( sTfR ) were measured by high performance liquid chromatography . Serum C - reactive protein ( CRP ) and hemoglobin ( HB ) were measured by radioimmunoturbidimetry , and the sTfR - SF index ( TFR - F index ) and total iron content were calculated .



Results : The prevalence of serum vitamin A and HB , SF , sTfR , TFR - F and serum iron content were ( 1 . 21 鹵 0 . 36 ) 渭mol / L , 0 . 17 ( p = 0.0011 ) , - 0 . 013 ( p = 0 . 7935 ) and - 0.05 ( p = 0.3652 ) . OR)(95% CI): 1.88(1.01, 2.97). If TFR - F was used as the criterion , VAD was not a risk factor for iron deficiency ( 95 % CI ) : 1.365 ( 0.286 , 6.513 ) , and the risk of anemia in VAD children was 2.56 times ( 95 % CI ) : 2.56 ( 1.15 , 5.70 ) , which was 2.56 times the risk of anemia in NVA children .



Conclusion :



The level of serum vitamin A in preschool children was closely related to the biochemical indexes reflecting the iron reserve and iron utilization of the organism , and there was no obvious relation between the iron absorption and the total iron content of the body .



2 VAD is an independent risk factor for the deficiency of iron storage , which may affect the iron absorption and iron utilization , and has little effect on iron absorption .



The 3 VAD is an independent risk factor for anemia , which may affect iron metabolism , but may also act through other pathways .



Effect of Various Kinds of Trace Nutrients Intervention on the Steady State of Iron Metabolism in the Second Part of Vitamin A



Objective : To observe the effects of vitamin A supplementation , vitamin A + iron and multiple trace nutrients supplementation on iron metabolism related biochemical indexes , and to evaluate the protective effects of different intervention methods on anemia and iron deficiency .



Methods : The level of serum vitamin A , serum ferritin ( SF ) level , serum C - reactive protein ( SF ) level , serum C - reactive protein ( SF ) level , serum C - reactive protein ( SF ) level , serum C - reactive protein ( SF ) level , serum C - reactive protein ( SF ) level , serum C - reactive protein ( CRP ) level and total iron content were measured by high performance liquid chromatography .



Results : There was no significant difference in the levels of serum levels of vitamin A ( P < 0 . 05 ) , but there was no significant difference in the levels of vitamin A + iron ( P < 0 . 05 ) . However , there was no significant difference in the levels of vitamin A + iron ( P < 0 . 05 ) .



Conclusion :



1 Vitamin A intervention had an impact on iron reserves and iron utilization .



There was no obvious effect on TFR - F index and total iron content of the body , indicating that vitamin A had no obvious effect on the absorption of iron in intestinal tract .



3 . The supplements of vitamin A and iron supplements may be a good way to improve the state of iron storage deficiency .



Effect of the third part of vitamin A nutritional status on iron regulation mode and its related mechanism



Objective : To investigate the effects of various components of iron responsive element - iron regulated protein ( IRE - IRPs ) on liver mRNA and protein level in rats with different vitamin A nutritional status and their effects on iron responsive element - iron regulated protein ( IRE - IRPs ) and hepcidin - ferroportin ( Hepc - FPN ) .



Methods : 30 healthy female Wistar rats were randomly divided into three groups : 1 ) normal vitamin A status ( NVA ) ( 10 rats ) , vitamin A deficiency rats ( vitamin A 400IU / kg ) .



Results : ( 1 ) There was no significant difference ( p < 0.05 ) between group A and VAD group ( p < 0.05 ) . There was no significant difference between the two groups ( p < 0.05 ) .



Conclusion :



In the absence of vitamin A , peripheral blood was mainly the low - pigment expression of small cells , and vitamin A supplementation could restore the above - mentioned changes ; vitamin A deficiency had little effect on average hemoglobin concentration and mean hemoglobin concentration ;



2 The nutritional status of different vitamin A has an obvious effect on the Hepc - FPN model of iron metabolism , and its possible pathway is to regulate the production of IL - 6 and BMP - 4 from the level of transcription , thus affecting the synthesis of hepcidin ;



3 The nutritional status of different vitamin A has an obvious effect on the IRE - IRPs model of iron metabolism , and one of the possible ways is by regulating the synthesis of IRPs - 1 from the transcription level .

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2009
【分類號(hào)】：R341

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 李廷玉,劉友學(xué),翟平,黎海芪,鄭惠連;維生素A缺乏模型研制[J];中國(guó)兒童保健雜志;1995年01期

2 李廷玉,瞿平,劉友學(xué),王亞平,黎海芪,鄭惠連;維生素A和鐵缺乏對(duì)大鼠紅系造血影響的比較[J];中國(guó)兒童保健雜志;1995年02期

3 練雪梅,李廷玉,瞿平,劉友學(xué);每周補(bǔ)充維生素A及每周補(bǔ)鐵對(duì)學(xué)齡前兒童貧血的干預(yù)試驗(yàn)[J];中國(guó)兒童保健雜志;2002年06期

4 李廷玉,王蓉,趙勇,瞿平,楊耀煌,練雪梅,毛春婷,戴英,劉友學(xué);不同劑量維生素A強(qiáng)化餅干對(duì)學(xué)齡前兒童健康影響的研究[J];中國(guó)兒童保健雜志;2004年01期

5 劉瑜，，李廷玉，王亞平，姜蓉，瞿平;維生素A缺乏對(duì)紅系早期祖細(xì)胞增殖影響的研究[J];重慶醫(yī)科大學(xué)學(xué)報(bào);1998年01期

6 李廷玉,楊莉,王亞平,王勇;維生素A對(duì)小鼠造血微環(huán)境影響的研究[J];營(yíng)養(yǎng)學(xué)報(bào);1999年04期

7 李廷玉,馮濤,王亞平,劉瑜,程茜,黎海芪;邊緣型維生素A缺乏對(duì)大鼠紅系細(xì)胞膜N糖鏈的影響[J];營(yíng)養(yǎng)學(xué)報(bào);1997年03期

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