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鋁暴露致大鼠貧血的機制

發(fā)布時間:2019-06-02 01:46
【摘要】: 將100只4周齡清潔級Wistar大鼠隨機均分為染鋁組(430mg·L-1,AI3+)與對照組(蒸餾水),設(shè)立5個觀測點,每隔30d處死染鋁大鼠和對照大鼠各10只。記錄大鼠臨床癥狀和體重變化;檢測大鼠血液象和網(wǎng)織紅細胞數(shù);血清中鋁、鐵、銅、鋅、鎂、鈣、磷、總膽紅素、間接膽紅素、一氧化氮(NO)和促紅細胞生成素(EPO)含量;血漿中轉(zhuǎn)鐵蛋白(TF)、總鐵結(jié)合力(TIBC)及可溶性轉(zhuǎn)鐵蛋白受體(sTFR)的含量;紅細胞膜超氧化物歧化酶(SOD)、過氧化氫酶(CAT)、谷胱甘肽過氧化物酶(GSH-Px)活性及丙二醛(MDA)的含量,紅細胞膜流動性,紅細胞膜ATP酶活性和唾液酸(SA)含量,紅細胞膜蛋白百分含量和分子量,并對大鼠骨髓顯微結(jié)構(gòu)及超微結(jié)構(gòu)進行觀察。結(jié)果表明: 1大鼠灌胃結(jié)晶三氯化鋁的LD50為1283.60 mg/kg體重,其95%可信限為1181.21-1394.86mg/kg體重,以430mg/L(Al3+)飲水染鋁可成功復(fù)制鋁中毒大鼠模型。 2隨染鋁時間的延長,大鼠紅細胞數(shù)、血紅蛋白含量(Hb)、紅細胞平均體積(MCV)、紅細胞平均血紅蛋白含量(MCH)、平均血球血紅蛋白濃度(MCHC)均逐漸降低,呈攝鋁時間-效應(yīng)關(guān)系,且顯著低于對照組(p0.05;p0.01),隨染鋁時間延長而加重,說明染鋁可致小細胞低色素性貧血。 3隨染鋁時間的延長,大鼠網(wǎng)織紅細胞數(shù)逐漸降低,呈攝鋁時間-效應(yīng)關(guān)系,且顯著低于對照大鼠(p0.05;p0.01),說明鋁可抑制大鼠的造血功能。 4隨染鋁時間的延長,大鼠棘形紅細胞數(shù)、血清總膽紅素及間接膽紅素含量逐漸升高,呈染鋁時間-效應(yīng)關(guān)系,且顯著高于對照組(p0.05;p0.01),說明鋁可致大鼠溶血。 5隨染鋁時間的延長,大鼠血清Al、Ca、Zn含量逐漸升高,且顯著高于對照組(p0.05;190.01),Cu、P含量逐漸降低,顯著低于對照組(p0.05;p0.01),且隨染鋁時間延長而加重,呈現(xiàn)染鋁時間-效應(yīng)苯系,說明鋁可致礦物質(zhì)元素代謝紊亂。 6隨染鋁時間的延長,大鼠血漿Fe含量先降低后升高,與對照組相比亦如此,且差異顯著(p0.05;p0.01);Al/Fe和TIBC逐漸升高,且顯著高于對照組(p0.05;p0.01);TF和sTFR含量均降低,且顯著低于對照組(p0.05;p0.01),骨髓細胞內(nèi)鐵含量升高,出現(xiàn)環(huán)形鐵粒,并隨染鋁時間延長而加重,呈現(xiàn)染鋁時間-效應(yīng)關(guān)系,說明鋁可影響鐵穩(wěn)態(tài)。 7隨染鋁時間的延長,大鼠血漿促紅細胞生成素和·氧化氮(NO)含量逐漸升高,呈染鋁時間-效應(yīng)關(guān)系,且顯著高于對照組(p0.05;p0.01),說明鋁可影響紅系細胞造血調(diào)控。 8隨染鋁時間的延長,大鼠紅細胞膜SOD、CAT、GSH-Px活性逐漸降低,且顯著低于對照組(p0.05;p0.01),MDA含量逐漸升高,且顯著高于對照組(p0.05;p0.01),并隨染鋁時間延長而加重,呈現(xiàn)染鋁時間-效應(yīng)關(guān)系,說明染鋁大鼠紅細胞抗氧化能力減弱,脂質(zhì)過氧化反應(yīng)增強。 9隨染鋁時間的延長,大鼠紅細胞膜ATPase活性逐漸減弱,呈染鋁時間-效應(yīng)關(guān)系,且顯著低于對照組(p0.05;p0.01),說明鋁可抑制大鼠紅細胞膜內(nèi)外離子交換。 10隨染鋁時間的延長,大鼠紅細胞膜熒光偏振度(P)和微粘度(η)降低,呈染鋁時間-效應(yīng)關(guān)系,且顯著低于對照組(p0.05;p0.01),說明染鋁可致大鼠紅細胞膜的流動性下降。 11隨染鋁時間的延長,大鼠紅細胞膜蛋白比例發(fā)生改變,蛋白區(qū)帶Ⅰ、Ⅱ百分含量逐漸升高,帶Ⅲ、Ⅴ、Ⅵ百分含量逐漸降低,呈染鋁時間-效應(yīng)關(guān)系,且顯著低于對照組(p0.05;p0.01),而帶Ⅳ無顯著變化;鋁暴露大鼠帶Ⅰ、Ⅴ、Ⅵ分子量降低,帶Ⅱ、Ⅲ、Ⅶ分子量增大,染鋁時間-效應(yīng)關(guān)系,且與對照相比差異顯著(p0.01),說明鋁暴露可影響大鼠紅細胞膜蛋白百分含量和分子量。 12紅細胞血涂片觀察可見,鋁暴露大鼠外周紅細胞變小,隨著攝鋁時間的延長,棘形紅細胞數(shù)顯著增多,呈染鋁時間-效應(yīng)關(guān)系,且顯著高于對照組(p0.05;p0.01),說明鋁可導(dǎo)致溶血。光鏡觀察可見,攝鋁大鼠骨髓中脂滴明顯增多,骨髓細胞數(shù)減少,說明鋁可抑制骨髓造血活動;電鏡觀察可見,攝鋁大鼠骨髓中血竇內(nèi)皮不完整,內(nèi)皮細胞核周隙增大,線粒體空泡化;紅系造血島中吞噬細胞線粒體空泡化,吞噬小體減少,說明鋁可抑制骨髓造血活動。
[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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