全氟辛烷磺酸对大鼠的肝肾毒性及番茄红素的保护作用

发布时间：2018-11-16 20:08

【摘要】： 目的: 观察亚慢性全氟辛烷磺酸(PFOS)对大鼠肝肾的毒性影响,探讨番茄红素(LP)对PFOS致肝肾毒性的保护作用;为阐明PFOS肝肾毒作用及机制、拓展番茄红素的应用范围提供科学依据。方法: 3月龄清洁级SD(sprague dawley,SD)大鼠48只,雌雄各半,随机分为8组:溶剂对照组、低剂量PFOS染毒组、中剂量PFOS染毒组、高剂量PFOS染毒、LP保护组、LP保护低剂量PFOS染毒组、LP保护中剂量PFOS染毒组、LP保护高剂量PFOS染毒组;溶剂对照组和LP保护组均进食2%Tween-80处理后的饲料,实验组分别进食低、中、高剂量(5、25、125mg/kgPFOS)的染毒饲料,溶剂对照组和各实验组分别灌胃1%CMC-Na溶液, LP保护组和LP保护低、中、高剂量PFOS染毒组灌胃20mg/kg·bw LP混悬液,每天灌胃一次,一周五天,连续进行2个月;末次灌胃24h后,眼眶静脉丛取血后处死大鼠,采用全自动生化分析仪检测血清ALT、ASP、AST、UREA、CRE、UA的含量;取肝脏、肾脏计算脏器系数;常规病理学切片,HE染色观察肝脏和肾脏组织形态学变化;制备肝脏和肾脏匀浆,采用DTNB法或Nitrite-kit法测定上清液中GSH、MDA含量和GSH-Px、SOD活性。结果:生发中心和边缘区模糊;红细胞增多,脾窦充血,白髓,红髓之间界限模糊。 1.中、高剂量PFOS染毒大鼠的体重增长低于溶剂对照组,且随PFOS剂量的增加,其抑制体重增加越明显(P0.05);而经LP保护的大鼠的体重增量与同剂量PFOS组相比有所提高,但无统计学意义(P0.05)。 2.中、高剂量PFOS组大鼠肝脏、肾脏系数低于溶剂对照组(P0.05),并呈剂量效应关系;加入LP保护剂后LP保护中、高剂量PFOS肝脏、肾脏脏器系数与相同剂量PFOS染毒组相比升高,差异有统计学意义(P0.05)。 3.肝组织切片显示,与溶剂对照组和LP保护组比较,低剂量PFOS染毒组肝组织形态结构无明显变化,而中、高剂量PFOS染毒组出现明显的肝细胞水肿和弥漫性脂肪变性,但经LP保护后仅出现轻度的气球样变和胞浆疏松化。肾组织切片显示,与溶剂对照组和LP保护组比较,低剂量PFOS组肾组织形态结构无明显变化,而中、高剂量PFOS组出现明显的管型和蛋白物质渗出,但经LP保护时仅出现少数炎性细胞浸润。 4.与溶剂对照组比较,经中、高剂量的PFOS染毒大鼠血清的ALT、ASP、AST、CREA、UREA及UA增高,差异有统计学意义(P0.05);但同时经LP保护的PFOS染毒大鼠血清的ALT、ASP、AST、CREA、UREA及UA均低于相同剂量PFOS染毒大鼠,差异有统计学意义(P0.05)。 5.与溶剂对照组比较,经中、高剂量的PFOS染毒大鼠肝肾组织匀浆液中的MDA、GSH含量增高,GSH-Px、SOD活力下降(P0.05);经LP保护的PFOS染毒大鼠组织匀浆液中的MDA、GSH含量降低, GSH-Px、SOD活力增高,差异有统计学意义(P0.05)。结论: 1.亚慢性全氟辛烷磺酸(PFOS)可致SD大鼠肝肾损伤。 2. 20mg/Kg.bw剂量番茄红素(LP)可拮抗PFOS所致肝肾损伤。 3.抗氧化损伤是番茄红素拮抗PFOS致亚慢性肝肾损伤的重要机制。
[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.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363

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