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全氟辛烷磺酸對大鼠的肝腎毒性及番茄紅素的保護(hù)作用

發(fā)布時間:2018-11-16 20:08
【摘要】: 目的: 觀察亞慢性全氟辛烷磺酸(PFOS)對大鼠肝腎的毒性影響,探討番茄紅素(LP)對PFOS致肝腎毒性的保護(hù)作用;為闡明PFOS肝腎毒作用及機制、拓展番茄紅素的應(yīng)用范圍提供科學(xué)依據(jù)。 方法: 3月齡清潔級SD(sprague dawley,SD)大鼠48只,雌雄各半,隨機分為8組:溶劑對照組、低劑量PFOS染毒組、中劑量PFOS染毒組、高劑量PFOS染毒、LP保護(hù)組、LP保護(hù)低劑量PFOS染毒組、LP保護(hù)中劑量PFOS染毒組、LP保護(hù)高劑量PFOS染毒組;溶劑對照組和LP保護(hù)組均進(jìn)食2%Tween-80處理后的飼料,實驗組分別進(jìn)食低、中、高劑量(5、25、125mg/kgPFOS)的染毒飼料,溶劑對照組和各實驗組分別灌胃1%CMC-Na溶液, LP保護(hù)組和LP保護(hù)低、中、高劑量PFOS染毒組灌胃20mg/kg·bw LP混懸液,每天灌胃一次,一周五天,連續(xù)進(jìn)行2個月;末次灌胃24h后,眼眶靜脈叢取血后處死大鼠,采用全自動生化分析儀檢測血清ALT、ASP、AST、UREA、CRE、UA的含量;取肝臟、腎臟計算臟器系數(shù);常規(guī)病理學(xué)切片,HE染色觀察肝臟和腎臟組織形態(tài)學(xué)變化;制備肝臟和腎臟勻漿,采用DTNB法或Nitrite-kit法測定上清液中GSH、MDA含量和GSH-Px、SOD活性。 結(jié)果:生發(fā)中心和邊緣區(qū)模糊;紅細(xì)胞增多,脾竇充血,白髓,紅髓之間界限模糊。 1.中、高劑量PFOS染毒大鼠的體重增長低于溶劑對照組,且隨PFOS劑量的增加,其抑制體重增加越明顯(P0.05);而經(jīng)LP保護(hù)的大鼠的體重增量與同劑量PFOS組相比有所提高,但無統(tǒng)計學(xué)意義(P0.05)。 2.中、高劑量PFOS組大鼠肝臟、腎臟系數(shù)低于溶劑對照組(P0.05),并呈劑量效應(yīng)關(guān)系;加入LP保護(hù)劑后LP保護(hù)中、高劑量PFOS肝臟、腎臟臟器系數(shù)與相同劑量PFOS染毒組相比升高,差異有統(tǒng)計學(xué)意義(P0.05)。 3.肝組織切片顯示,與溶劑對照組和LP保護(hù)組比較,低劑量PFOS染毒組肝組織形態(tài)結(jié)構(gòu)無明顯變化,而中、高劑量PFOS染毒組出現(xiàn)明顯的肝細(xì)胞水腫和彌漫性脂肪變性,但經(jīng)LP保護(hù)后僅出現(xiàn)輕度的氣球樣變和胞漿疏松化。腎組織切片顯示,與溶劑對照組和LP保護(hù)組比較,低劑量PFOS組腎組織形態(tài)結(jié)構(gòu)無明顯變化,而中、高劑量PFOS組出現(xiàn)明顯的管型和蛋白物質(zhì)滲出,但經(jīng)LP保護(hù)時僅出現(xiàn)少數(shù)炎性細(xì)胞浸潤。 4.與溶劑對照組比較,經(jīng)中、高劑量的PFOS染毒大鼠血清的ALT、ASP、AST、CREA、UREA及UA增高,差異有統(tǒng)計學(xué)意義(P0.05);但同時經(jīng)LP保護(hù)的PFOS染毒大鼠血清的ALT、ASP、AST、CREA、UREA及UA均低于相同劑量PFOS染毒大鼠,差異有統(tǒng)計學(xué)意義(P0.05)。 5.與溶劑對照組比較,經(jīng)中、高劑量的PFOS染毒大鼠肝腎組織勻漿液中的MDA、GSH含量增高,GSH-Px、SOD活力下降(P0.05);經(jīng)LP保護(hù)的PFOS染毒大鼠組織勻漿液中的MDA、GSH含量降低, GSH-Px、SOD活力增高,差異有統(tǒng)計學(xué)意義(P0.05)。 結(jié)論: 1.亞慢性全氟辛烷磺酸(PFOS)可致SD大鼠肝腎損傷。 2. 20mg/Kg.bw劑量番茄紅素(LP)可拮抗PFOS所致肝腎損傷。 3.抗氧化損傷是番茄紅素拮抗PFOS致亞慢性肝腎損傷的重要機制。
[Abstract]:Objective: to observe the toxic effects of subchronic perfluorooctane sulfonic acid (PFOS) on liver and kidney in rats and to explore the protective effect of lycopene (LP) on hepatorenal toxicity induced by PFOS. In order to elucidate the toxic effect and mechanism of PFOS liver and kidney and expand the application range of lycopene, it provides scientific basis. Methods: Forty-eight 3-month-old clean grade SD (sprague dawley,SD rats were randomly divided into 8 groups: solvent control group, low dose PFOS group, middle dose PFOS group, high dose PFOS group and LP protection group. LP protected low dose PFOS group, LP protected medium dose PFOS group, LP protected high dose PFOS group. Both the solvent control group and the LP protection group were fed with 2%Tween-80 treated diets. The experimental groups were fed with low, medium and high doses (525 125 mg / kg PFOS) respectively. The solvent control group and the experimental groups were fed with 1%CMC-Na solution respectively. The LP protection group and the LP protection group were low, medium and high dose PFOS groups were given 20mg/kg bw LP suspension once a day, five days a week for 2 months; 24 hours after the last gastric perfusion, the rats were killed after blood extraction from the orbital venous plexus, the serum ALT,ASP,AST,UREA,CRE,UA content was detected by automatic biochemical analyzer, and the organ coefficients of liver and kidney were calculated. The histomorphologic changes of liver and kidney were observed by HE staining, and the content of GSH,MDA and the activity of GSH-Px,SOD in supernatant were determined by DTNB or Nitrite-kit method. Results: the germinal center and marginal area were blurred, and the boundary between erythrocytosis, splenic sinus congestion, white pulp and red pulp was blurred. 1. The weight gain of high dose PFOS exposed rats was lower than that of solvent control group, and with the increase of PFOS dose, the inhibition weight increased significantly (P0.05). The weight increment of LP protected rats was higher than that of the same dose PFOS group, but there was no statistical significance (P0.05). 2. The liver and kidney coefficients in the high dose PFOS group were lower than those in the solvent control group (P0.05). The organ coefficient of liver and kidney of high dose PFOS group was higher than that of the same dose of PFOS group after LP was added to the protective agent (P0.05). 3. Compared with the solvent control group and the LP protection group, the liver tissue morphology in the low dose PFOS group showed no significant change, while in the middle and high dose PFOS group there was obvious hepatocyte edema and diffuse steatosis. However, only mild balloon degeneration and cytoplasmic loosening were observed after LP protection. Renal tissue sections showed that compared with solvent control group and LP protection group, there was no significant change in renal tissue morphology in low dose PFOS group, while significant exudation of tubular and protein substances appeared in middle and high dose PFOS group. However, only a few inflammatory cells were infiltrated by LP. 4. Compared with the solvent control group, the serum ALT,ASP,AST,CREA,UREA and UA of rats exposed to high dose of PFOS were significantly higher than those of the control group (P0.05). At the same time, the ALT,ASP,AST,CREA,UREA and UA of PFOS exposed to PFOS treated with LP were lower than that of rats exposed to PFOS at the same dose, the difference was statistically significant (P0.05). 5. Compared with the solvent control group, the content of MDA,GSH in the liver and kidney homogenate was increased and the activity of GSH-Px,SOD was decreased (P0.05) in the liver and kidney homogenate of the rats exposed to high dose of PFOS (P0.05). The content of MDA,GSH in tissue homogenate of PFOS exposed to LP was decreased and the activity of GSH-Px,SOD was increased (P0.05). Conclusion: 1. Subchronic perfluorooctane sulfonic acid (PFOS) can induce liver and kidney injury in SD rats. 2. 20mg/Kg.bw dose of lycopene (LP) could antagonize liver and kidney injury induced by PFOS. 3. Antioxidant damage is an important mechanism of lycopene antagonizing subchronic liver and kidney injury induced by PFOS.
【學(xué)位授予單位】:南華大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2010
【分類號】:R363

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