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铝暴露致大鼠贫血的机制

发布时间:2019-06-02 01:46
【摘要】: 将100只4周龄清洁级Wistar大鼠随机均分为染铝组(430mg·L-1,AI3+)与对照组(蒸馏水),设立5个观测点,每隔30d处死染铝大鼠和对照大鼠各10只。记录大鼠临床症状和体重变化;检测大鼠血液象和网织红细胞数;血清中铝、铁、铜、锌、镁、钙、磷、总胆红素、间接胆红素、一氧化氮(NO)和促红细胞生成素(EPO)含量;血浆中转铁蛋白(TF)、总铁结合力(TIBC)及可溶性转铁蛋白受体(sTFR)的含量;红细胞膜超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)的含量,红细胞膜流动性,红细胞膜ATP酶活性和唾液酸(SA)含量,红细胞膜蛋白百分含量和分子量,并对大鼠骨髓显微结构及超微结构进行观察。结果表明: 1大鼠灌胃结晶三氯化铝的LD50为1283.60 mg/kg体重,其95%可信限为1181.21-1394.86mg/kg体重,以430mg/L(Al3+)饮水染铝可成功复制铝中毒大鼠模型。 2随染铝时间的延长,大鼠红细胞数、血红蛋白含量(Hb)、红细胞平均体积(MCV)、红细胞平均血红蛋白含量(MCH)、平均血球血红蛋白浓度(MCHC)均逐渐降低,呈摄铝时间-效应关系,且显著低于对照组(p0.05;p0.01),随染铝时间延长而加重,说明染铝可致小细胞低色素性贫血。 3随染铝时间的延长,大鼠网织红细胞数逐渐降低,呈摄铝时间-效应关系,且显著低于对照大鼠(p0.05;p0.01),说明铝可抑制大鼠的造血功能。 4随染铝时间的延长,大鼠棘形红细胞数、血清总胆红素及间接胆红素含量逐渐升高,呈染铝时间-效应关系,且显著高于对照组(p0.05;p0.01),说明铝可致大鼠溶血。 5随染铝时间的延长,大鼠血清Al、Ca、Zn含量逐渐升高,且显著高于对照组(p0.05;190.01),Cu、P含量逐渐降低,显著低于对照组(p0.05;p0.01),且随染铝时间延长而加重,呈现染铝时间-效应苯系,说明铝可致矿物质元素代谢紊乱。 6随染铝时间的延长,大鼠血浆Fe含量先降低后升高,与对照组相比亦如此,且差异显著(p0.05;p0.01);Al/Fe和TIBC逐渐升高,且显著高于对照组(p0.05;p0.01);TF和sTFR含量均降低,且显著低于对照组(p0.05;p0.01),骨髓细胞内铁含量升高,出现环形铁粒,并随染铝时间延长而加重,呈现染铝时间-效应关系,说明铝可影响铁稳态。 7随染铝时间的延长,大鼠血浆促红细胞生成素和·氧化氮(NO)含量逐渐升高,呈染铝时间-效应关系,且显著高于对照组(p0.05;p0.01),说明铝可影响红系细胞造血调控。 8随染铝时间的延长,大鼠红细胞膜SOD、CAT、GSH-Px活性逐渐降低,且显著低于对照组(p0.05;p0.01),MDA含量逐渐升高,且显著高于对照组(p0.05;p0.01),并随染铝时间延长而加重,呈现染铝时间-效应关系,说明染铝大鼠红细胞抗氧化能力减弱,脂质过氧化反应增强。 9随染铝时间的延长,大鼠红细胞膜ATPase活性逐渐减弱,呈染铝时间-效应关系,且显著低于对照组(p0.05;p0.01),说明铝可抑制大鼠红细胞膜内外离子交换。 10随染铝时间的延长,大鼠红细胞膜荧光偏振度(P)和微粘度(η)降低,呈染铝时间-效应关系,且显著低于对照组(p0.05;p0.01),说明染铝可致大鼠红细胞膜的流动性下降。 11随染铝时间的延长,大鼠红细胞膜蛋白比例发生改变,蛋白区带Ⅰ、Ⅱ百分含量逐渐升高,带Ⅲ、Ⅴ、Ⅵ百分含量逐渐降低,呈染铝时间-效应关系,且显著低于对照组(p0.05;p0.01),而带Ⅳ无显著变化;铝暴露大鼠带Ⅰ、Ⅴ、Ⅵ分子量降低,带Ⅱ、Ⅲ、Ⅶ分子量增大,染铝时间-效应关系,且与对照相比差异显著(p0.01),说明铝暴露可影响大鼠红细胞膜蛋白百分含量和分子量。 12红细胞血涂片观察可见,铝暴露大鼠外周红细胞变小,随着摄铝时间的延长,棘形红细胞数显著增多,呈染铝时间-效应关系,且显著高于对照组(p0.05;p0.01),说明铝可导致溶血。光镜观察可见,摄铝大鼠骨髓中脂滴明显增多,骨髓细胞数减少,说明铝可抑制骨髓造血活动;电镜观察可见,摄铝大鼠骨髓中血窦内皮不完整,内皮细胞核周隙增大,线粒体空泡化;红系造血岛中吞噬细胞线粒体空泡化,吞噬小体减少,说明铝可抑制骨髓造血活动。
[Abstract]:One hundred and four-week-old Wistar rats were randomly divided into two groups (430 mg 路 L-1, AI3 +) and control group (distilled water),5 observation points were set up, and 10 rats and control rats were sacrificed every 30 days. The clinical symptoms and body weight changes of the rats were recorded; the blood and reticulocytes in the rat were detected; the contents of aluminum, iron, copper, zinc, magnesium, calcium, phosphorus, total bilirubin, indirect bilirubin, nitric oxide (NO), and erythropoietin (EPO) in the serum were measured; and the plasma (TF), the content of the total iron binding force (TIBC) and the soluble transferrin receptor (sTFR), the content of the superoxide dismutase (SOD), the catalase (CAT), the glutathione peroxidase (GSH-Px) activity and the malondialdehyde (MDA) in the erythrocyte membrane, the fluidity of the erythrocyte membrane, The activity of erythrocyte membrane ATPase and the content of sialic acid (SA), the percentage of red blood cell membrane protein and the molecular weight were observed, and the microstructure and ultrastructure of the bone marrow of the rat were observed. The results show that: The LD50 of the three-aluminum chloride in the rat was 1283.60mg/ kg, the 95% confidence limit was 1181.21-1394.86 mg/ kg body weight, and the aluminum-poisoned rats were successfully copied with 430 mg/ L (Al3 +) drinking water. The mean corpuscular hemoglobin concentration (MCH) and the mean corpuscular hemoglobin concentration (MCHC) of the rat were gradually decreased with the time of Al-dyeing, and the mean corpuscular hemoglobin concentration (MCH) and the mean corpuscular hemoglobin concentration (MCHC) decreased gradually. -effect relationship, and was significantly lower than that of the control group (p0.05; p0.01), which was aggravated with the extension of the aluminum time, indicating that the small cells could be caused by the staining of the aluminum. The number of reticulocytes in the rat decreased gradually, and the time-effect relationship was significantly lower than that of the control rats (p0.05; p0.01), indicating that the aluminum can be suppressed. The hemopoietic function of the rat was increased with the prolongation of the time of the staining of the aluminum, the number of the acanthous red blood cells, the total bilirubin and the indirect bilirubin in the rats, the time-effect relationship of the staining and the time-effect of the staining, and was significantly higher than that of the control group (p0.05; p0.01). The results showed that the content of Al, Ca and Zn in the serum of the rats was higher than that of the control group (p0.05; p0.01), and the content of Cu and P in the rats was significantly lower than that of the control group (p0.05; p0.01), and the content of Al, Ca and Zn in the rats was significantly lower than that of the control group (p0.05; p0.01), and the time of Al-staining was prolonged. aggravated by the presence of an aluminum-affected time-effect benzene series, However, that content of Fe and TBC in the rat was significantly higher than that in the control group (p0.05; p0.01); both the content of TF and sTFR were higher than that in the control group (p0.05; p0.01). The content of iron in the bone marrow cells was increased, and the iron content of the bone marrow cells was increased. The time-effect relationship indicated that the aluminum can influence the steady state of iron. The contents of plasma erythropoietin and nitric oxide (NO) in the rats were increased gradually with the time of the Al-staining, and the time-effect of the staining was significantly higher than that in the control group (p0.05; p The results showed that the activity of SOD, CAT and GSH-Px in the erythrocyte membrane of the rat was lower than that of the control group (p0.05; p0.01), and the content of MDA was higher than that of the control group (p0.05; p0.01). And the time-effect relationship of the aluminum and aluminum is presented and the dyeing and dyeing time-effect relation is described. The anti-oxidation ability of red blood cells in aluminum rats was decreased, and the lipid peroxidation was enhanced. The activity of ATPase in erythrocyte membrane of the rat was gradually decreased with the time of Al-staining, and the time-effect of the staining was significantly lower than that in the control group (p0.05). (P) and microviscosity (P) of the red cell membrane of the rat decreased with the time of the Al-staining, and the time-effect of the staining was significantly lower than that of the control group (p0). (.05; p0.01), indicating that the fluidity of the red cell membrane of the rat can be reduced, the proportion of the red blood cell membrane protein of the rat changes, the percentage content of the protein zone I and II is gradually increased, the percentage content of the bands III, V, and VI is gradually reduced, The time-effect relationship of Al-exposed rats was significantly lower than that of the control group (p0.05; p0.01), and the band 鈪,

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