氟化钠亚慢性染毒致大鼠肺毒性机制的初步研究

A preliminary study on the mechanism of lung toxicity of sub-chronic exposure to sodium fluoride in rats

目的 研究不同染毒剂量的氟化钠亚慢性染毒与大鼠肺组织病理学改变之间的关系,探讨氟化钠致大鼠肺组织损伤的效应及相关机制。方法 32只Wistar健康雄性大鼠随机分为对照组、低剂量组、中剂量组和高剂量组,每组8只,分别给予0、12、24、48 mg/(kg·d)氟化钠水溶液灌胃,实验周期16周。记录各组大鼠氟牙症发生情况、体质量变化,计算各组大鼠肺系数,采用苏木精-伊红(HE)染色观察肺组织病理学变化,采用酶联免疫吸附实验(ELISA)测定血清超氧化物歧化酶(SOD)、丙二醛(MDA)含量,采用TUNEL染色法评估肺脏细胞凋亡水平,并通过免疫组化检测肺组织天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)蛋白表达水平。结果 染毒结束后,低、中、高剂量组大鼠上、下颌切牙呈不同程度的氟牙症改变;高剂量组大鼠体质量增加量低于其余3组(P<0.05);高剂量组大鼠肺系数及血清中MDA含量均高于对照组(P<0.05);低、中、高剂量组大鼠均出现不同程度的肺间质炎症浸润及肺泡形态学改变;与对照组相比,低、中、高组大鼠的肺组织细胞凋亡率和Caspase-3蛋白表达升高,差异有统计学意义(P <0.05)。结论 氟化钠亚慢性染毒可使大鼠肺组织出现损伤效应,其机制可能与氧化应激诱导的细胞凋亡有关。

Objective To study the relationship between different doses of subchronic sodium fluoride exposure and lung histopathological changes in rats,and to explore the effect and related mechanism of sodium fluoride induced lung tissue injury in rats.Methods Thirty-two Wistar male rats were randomly divided into control,low,medium and high dose groups,each group included 8 rats,intragastric administration of sodium fluoride toxin solution 0,12,24,and 48 mg/(kg·d).The experiment lasted for 16 weeks.The incidence of dental fluorosis and weight in each group of rats was recorded,the lung coefficient was calculated,the pathological changes of lung tissue was observed by HE staining,enzyme-linked immunosorbent assay(ELISA)was used to detect the content of superoxide dismutase(SOD)and malondialdehyde(MDA)levels in rats serum,apoptosis level of lung cells was assessed by TUNEL staining,and the Caspase-3 protein expression levels in lung tissues were determined by immunohistochemistry.Results At the end of exposure,the upper and lower incisors of rats in different dose groups showed different degrees of dental fluorosis.The increase in body weight of the rats in the high-dose group was lower than that in the other three groups(P<0.05).The coefficient of lung organs and the content of MDA in serum of the rats in the high-dose group were higher than those in the control group(P<0.05).The rats in the low,medium and high dose groups had different degrees of pulmonary interstitial inflammatory infiltration and alveolar morphological changes.Compared with the control group,the lung cell apoptosis rate and Caspase-3 protein expression of the rats in the low,middle and high groups significantly increased,and the differences were statistically significant(P<0.05).Conclusion Subchronic exposure to sodium fluoride can cause the lung tissue damage in rats,and the mechanism may be related to the apoptosis induced by oxidative stress.