大鼠氟中毒对肾功能损害的实验研究

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目的:用腹腔注射氟化钠水溶液的方法建立大鼠急性氟中毒模型,检测氟中毒大鼠肾脏TGF-β1的表达,探讨TGF-β1在氟中毒肾脏损害表达的意义。方法:健康成年SD大鼠,分为高氟组(20 mg/kg),低氟组12只(10 mg/kg),生理盐水对照组12只。腹腔注射给药,30 d后测定各组大鼠体重差、肾重/体重比,氟中毒大鼠尿常规变化,氟中毒大鼠肾功能变化;离子电极法测量尿氟浓度,测量骨氟浓度,免疫组化方法检测肾脏TGF-β1分布和含量,HE染色方法显微镜下观察大鼠肾组织结构病理学改变。结果:大鼠牙齿呈黄白相间的氟中毒体症,随染氟剂量的增高,尿氟和骨氟浓度增高,各组差异显著(P<0.05);各组大鼠体重差、肾重/体重比,氟中毒大鼠尿常规变化,氟中毒大鼠肾功能变化,各组间未有明显差异(P>0.05);与对照组比较,染氟大鼠肾小管上皮细胞水肿、渗出、坏死,细胞间界限不清,且随着染氟浓度增高,损伤改变加重,肾小球和肾间质改变轻微;随着染毒浓度增高,TGF-β1在肾小管上皮细胞的胞质中表达增强,与对照组相比,差异显著(P<0.01)。结论:氟中毒可引起肾结构损伤,主要表现为肾小管上皮细胞损伤;氟中毒TGF-β1主要在大鼠肾脏肾小管表达,可能是肾小管损伤与修复过程中的一对重要互逆平衡因素;在肾功能出现损害前,TGF-β1可以早期判断氟对肾脏集合系统损害。 OBJECTIVE: To establish acute fluorosis model in rats by intraperitoneal injection of sodium fluoride aqueous solution and to detect the expression of TGF-β1 in the kidney of fluorosis rats and to explore the significance of TGF-β1 expression in renal damage induced by fluoride poisoning. Methods: Healthy adult SD rats were divided into high fluoride group (20 mg / kg), low fluoride group (12 mg / kg) and saline group (12). After 30 days, the body weight, kidney weight / body weight ratio of rats in each group, urine routine changes in rats with fluorosis and renal function in rats with fluorosis were measured. Urinary fluoride concentration was measured by iontophoresis, , The distribution and content of TGF-β1 in kidneys were detected by immunohistochemistry, and the histopathological changes in rat kidneys were observed by HE staining. Results: The teeth of rats were yellow-and-white fluorosis. The levels of urinary fluoride and bone fluoride increased with the increase of fluoride dose (P <0.05). The body weight, kidney weight / body weight Compared with the control group, the changes of urinary routine in rats with fluorosis and the changes of renal function in fluorosis rats showed no significant difference among the groups (P> 0.05). Compared with the control group, the renal tubular epithelial cells in the fluoride-exposed rats had edema, exudation and necrosis , With unclear boundaries between cells. With the increase of fluoride concentration, the changes of injury were aggravated and the changes of glomerulus and renal interstitium were slight. The expression of TGF-β1 was enhanced in the cytoplasm of renal tubular epithelial cells , Compared with the control group, the difference was significant (P <0.01). Conclusion: Fluorosis can cause renal structural damage, which is mainly manifested as renal tubular epithelial cell injury. The expression of TGF-β1 in renal tubular tissue of rats with fluorosis is probably an important reciprocal balance factor in the process of renal tubular injury and repair ; Before renal damage, TGF-β1 can early determine the fluorine damage to the renal collecting system.
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