【作者】 王平贵；

【导师】 张本忠； 王俊玲；

【作者基本信息】 兰州大学 ， 卫生毒理学， 2009， 硕士

【摘要】 目的:1、观察氟及氟铝联合作用对大鼠体重增长和肝肾脏器系数的影响;2、探讨氟及氟铝联合作用对大鼠血常规和血生化指标的影响;3、分析慢性氟中毒对大鼠肾功能的影响及其与氧化应激的关系;4、探讨慢性氟中毒对大鼠肝、肾组织形态的影响。方法:健康Wistar大鼠56只随机分为7组,每组8只,给予不同剂量的氟化钠和三氯化铝,氟铝联合剂量分别为（0+0）、（100+0）、（200+0）、（300+0）、（100+10）、（200+10）、（300+10）mg/L。灌胃染毒96天,每周称量体重一次,染毒结束次日眼球采血,颈椎脱位法处死,取肝、肾称重,计算脏器系数;眼球采血40μl,血样加抗凝剂乙二氨四乙酸二钠（EDTA-Na₂）即时检测血常规:红细胞数（RBC）、红细胞平均容积（MCV）、白细胞数（WBC）、血红蛋白（HGB）、红细胞比积（HCT）、平均红细胞血红蛋白含量（MCH）、平均红细胞血红蛋白浓度（MCHC）、血小板数（PLT）、淋巴细胞数（LYM）、红细胞体积分布宽度（RDW）;眼球采血后静置,取60μl血清检测肝、肾功能生化指标:天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）、尿素（Urea）、肌酐（Cr）;取肾脏组织制备组织匀浆,试剂盒测定丙二醛（MDA）、一氧化氮（NO）含量以及过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）、一氧化氮合酶（NOS）活性;取肝、肾组织洗去血渍后甲醛固定,制作常规切片,HE染色,用光镜观察大鼠肝、肾的病理形态学变化。结果:1、大鼠体重随实验时间延长而明显增加（P＜0.001）,不同实验分组与实验时间有交互作用（P＜0.05）,而对照组及各染毒组间无显著性差异（P＞0.05）。氟及氟铝联合对大鼠肝肾脏器系数有一定的影响;2、与对照组相比,血常规指标中染毒组RBC显著增加（P＜0.05）,而MCV减小（P＜0.05）。血生化指标AST和Urea明显升高（P＜0.05或P＜0.01）;同时,在本实验条件下的部分结果提示氟铝联合作用存在一种趋势:氟铝在低剂量氟组中有协同作用而在高剂量氟组中有拮抗作用。3、肾脏组织中抗氧化酶CAT、GSH-Px和NOS活力降低,NO含量下降,而脂质过氧化产物MDA含量升高,差异有统计学意义（P＜0.05或P＜0.01）;4、光镜观察肝小叶轮廓欠清,窦组织细胞轻度增生,中央静脉及肝窦轻度扩张充血。肾脏近曲小管上皮细胞不同程度颗粒变性,部分空泡变性,间质小管轻度扩张充血。结论:1、氟及氟铝联合对大鼠体重无显著影响,但对肝肾脏器系数有一定的影响;2、氟及氟铝联合对大鼠血常规和肝、肾功能血生化指标有一定的影响,使大鼠红细胞增生而细胞体积变小,质量下降,而肝肾功能受损。铝对不同浓度氟的毒性效应具有不同的联合作用;3、慢性氟中毒对大鼠肾功能有一定损伤。氟使肾组织细胞氧化应激效应增强,抗氧化酶受抑制,可能是氟致大鼠肾脏组织细胞损伤的机制之一;4、慢性氟中毒对大鼠肝、肾组织形态有一定的影响。更多还原

【Abstract】 Objective:1.To observe the effects of fluorine and combination of aluminum and fluorine on body weight and organ coefficient of rats.2.To study the effects of fluorine and combination of aluminum and fluorine on index of blood routine and blood biochemistry of rats.3.To understand the effects of chronic fluorosis on renal function of rat and the relationship between oxidative stress of kidney.4.To study the effects of chronic fluorosis on morphologic changes of liver and kidney of rats.Methods:56 Wistar rats were randomly divided into 7 groups,and exposed to a series of doses of fluoride and aluminum(F+Al),which were(0+0),(100+0), (200+0),(300+0),(100+10),(200+10),and(300+10) mg/L.After 96 days intragastric administration,blood samples were collected on eyes of rats to determined blood routine:red blood cell(RBC),white blood cell(WBC),lymphocyte(LYM),platelet (PLT),hemoglobin(HGB),hematocrit(HCT),mean corpuscular hemoglobin(MCH), Mean corpuscular-hemoglobin concentration(MCHC),mean corpuscular volume (MCV),at the same time some blood biochemistry indicators related to functions of liver and kidney were determined such as aspartic acid aminotransferase(AST), alanine aminotransferase(ALT),alkaline phosphatase(ALP),Crea(Cr) and Urea. Organ coefficient of liver and kidney were calculated.The kidney homogenates were prepared to detect the content of malondialdehyde(MDA),nitric oxide(NO) and the activity of catalase(CAT),glutathione peroxidase(GSH-Px) and nitric oxide synthase (NOS).The tissues of livers and kidneys in experimental rats were fixed by formaldehyde after washing away the blood stains,and were made into conventional slice with HE staining.Pathological changes of rat kidney and liver were observed by light microscopy.Results:1.The body weight of rats are increasing with experimental time,while the control group and relapse group no significant difference.There is interaction between treating effectors and experimental time.2.Compared with the control group, the RBC of exposed groups obviously increased while the MCV remarkably diminished(P＜0.05),AST and Urea also significantly increased(P＜0.05 or P＜0.01). At the same time,the part of data under this experimental conditions suggest that there was a trend about the joint role of aluminum and fluoride:aluminum appears synergistic effect in the low-dose fluoride group while has antagonistic joint action in the high-dose group.3.Compared with the control group,the Urea of exposed groups obviously increased(P＜0.05).The activity of CAT,GSH-Px,NOS depressed,and the content of NO decreased while the content of MDA increased.There was a significant difference(P＜0.05 or P＜0.01).4.We can see by light microscope that the contour of hepatic lobule is unclear,the cells of sinus tissue are mild hyperplasia,and the central vein and hepatic sinusoid are mildly congestive and expanded.The epithelial cells of kidney proximal tubule are granular degeneration in varying degrees,some are vacuolar degeneration,and interstitial tubule are mildly congestive and expanded.Conclusion:1.The effects of and combination of aluminum and fluorine on body weight of rats are not significant,but they affect on organ coefficient of liver and kidney of rats to some extent.2.Fluorine and combination of aluminum and fluorine have toxicity on rats to a certain extent.The erythrocyte of rat are proliferated,while the cell size is made small and the cell quality is deteriorated,meanwhile functions of liver and kidney are impaired.Aluminum shows different joint action in different concentrations of fluorine.3.Chronic fluorosis have toxicity on renal function to a certain extent,and the increasing of oxidative stress and inhibition of antioxidant enzymes may be one of the mechanisms caused by fluoride in kidney tissue injury of rats.4.Chronic fluorosis have a certain morphological influence on liver and kidney of rats.更多还原