刘盈莹, 丁凡, 王若静, 吴璇, 张林, 吴庆. 环境高浓度多离子饮水和高温暴露诱导小鼠肾脏功能损伤[J]. 环境与职业医学, 2024, 41(5): 546-551, 559. DOI: 10.11836/JEOM23443
引用本文: 刘盈莹, 丁凡, 王若静, 吴璇, 张林, 吴庆. 环境高浓度多离子饮水和高温暴露诱导小鼠肾脏功能损伤[J]. 环境与职业医学, 2024, 41(5): 546-551, 559. DOI: 10.11836/JEOM23443
LIU Yingying, DING Fan, WANG Ruojing, WU Xuan, ZHANG Lin, WU Qing. Renal impairment in mice induced by environmental high concentration of polyionized drinking water and high temperature exposure[J]. Journal of Environmental and Occupational Medicine, 2024, 41(5): 546-551, 559. DOI: 10.11836/JEOM23443
Citation: LIU Yingying, DING Fan, WANG Ruojing, WU Xuan, ZHANG Lin, WU Qing. Renal impairment in mice induced by environmental high concentration of polyionized drinking water and high temperature exposure[J]. Journal of Environmental and Occupational Medicine, 2024, 41(5): 546-551, 559. DOI: 10.11836/JEOM23443

环境高浓度多离子饮水和高温暴露诱导小鼠肾脏功能损伤

Renal impairment in mice induced by environmental high concentration of polyionized drinking water and high temperature exposure

  • 摘要: 背景

    慢性肾病(CKD)的全球疾病负担日益严重。环境因素是不明原因慢性肾病(CKDu)的诱发因素之一。然而,饮用环境高浓度多离子水和高温暴露对肾脏功能的影响尚无确凿毒理学证据。

    目的

    初步探究饮用环境高浓度氟钙钠溴离子水和高温暴露对小鼠肾脏功能的影响。

    方法

    将雄性ICR小鼠(8周龄)随机分组。以3 mg·L−1氟离子、250 mg·L−1钙离子、400 mg·L−1钠离子和1 mg·L−1溴离子(模拟斯里兰卡CKDu高发地区地下水高浓度离子)及32 ℃高温建立小鼠饮水暴露模型,分为氟钙钠溴离子与高温混合暴露组,各离子和高温单独暴露组,氟钙钠离子暴露组,氟钙钠溴离子暴露组。对照组动物给予一般纯净水,正常室温环境(23±2) ℃。连续暴露12周后,测定体重和肝(肾)脏器系数,通过苏木精-伊红染色法(HE)染色和病理评分评估肾组织病理学损伤。收集暴露12周末的24 h尿,测定肌酐(UCr)、白蛋白(ALB)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和β2-微球蛋白(β2-MG)水平。使用TUNEL法检测细胞凋亡。

    结果

    与对照组相比,氟钙钠溴离子与高温混合暴露组的小鼠体重显著下降,肾组织病理学损伤评分和尿β2-MG水平均显著升高(P<0.05)。与对照组比较,氟钙钠溴离子暴露组(除β2-MG水平下降之外)和氟钙钠离子暴露组小鼠体重和尿中肾损伤指标差异无统计学意义(P>0.05),但肾脏组织病理学损伤评分增加(P<0.05)。然而,与对照组比,各离子单独饮水暴露组和高温单独处理组动物的体重、肝(肾)脏器系数、肾组织病理学损伤评分均无统计学差异(P>0.05)。氟钙钠离子暴露组与氟钙钠溴离子暴露组小鼠肾组织病理学损伤评分差异也无统计学意义(P>0.05)。溴离子与氟钙钠离子对肾组织病理损伤的交互作用无统计学意义(P>0.05)。TUNEL实验发现,氟钙钠离子暴露可诱导肾小管上皮细胞凋亡(P<0.05)。

    结论

    环境高浓度氟钙钠离子饮水混合暴露可导致肾脏组织病理损伤,高温单独暴露不影响肾脏组织病理损伤,但与高氟钙钠离子饮水混合暴露时可加剧肾小管功能损伤。

     

    Abstract: Background

    The burden of chronic kidney diseases (CKD) is continuously increasing in the globe. Environmental factors are one of the trigger factors for chronic kidney diseases of unknown etiology (CKDu). However, the current toxicological evidence on the renal effects induced by environmental high concentrations of multiple ions in drinking water and high temperature exposure is very limited.

    Objective

    To preliminary investigate the renal effects of exposure to drinking water with environmental high concentrations of fluoride, calcium, sodium, and bromide ions alone or in combination with high temperature in mice.

    Methods

    A mouse drinking water exposure model was established using ICR male mouse (8 weeks old) with exposure to 3 mg·L−1 fluoride ions, 250 mg·L−1 calcium ions, 400 mg·L−1 sodium ions, and 1 mg·L−1 bromide ions (to mimic the high concentration of ions in the groundwater in the areas with a high prevalence rate of CKDu in Sri Lanka) and high temperature of 32 ℃. ICR male mice were randomly divided into a mixed fluoride-calcium-sodium-bromide ion and high temperature exposure group, exposure groups of each ion and high temperature alone, a fluoride-calcium-sodium ion exposure group, and a fluoride-calcium-sodium-bromide ion exposure group. In the control group, the animals were given normal purified water at room temperature of (23±2) ℃. After 12 consecutive weeks of exposure, body weights and liver (kidney) organ coefficients were determined. Assessment of renal histopathologic damage was performed by hematoxylin-eosin staining and pathology scoring. At the end of the 12-week exposure period, 24 h urine samples were collected for the measurements of creatinine (UCr), albumin (ALB), neutrophil gelatinase-associated lipocalin (NGAL), and β2-microglobulin (β2-MG) levels. Cell apoptosis was assessed by TUNEL assay.

    Results

    The mice in the mixed exposure group showed a significant decrease in body weight and marked increases in the scores of renal histopathological injuries and the urinary levels of β2-MG compared to those of the control mice (P<0.05). Compared with the control group, the differences in body weight and urinary renal injury indexes of the mice in the fluoride-calcium-sodium and the fluoride-calcium-sodium-bromide ion groups (except for the decrease of the β2-MG levels in urinary in the latter group) were not statistically significant (P>0.05), but the renal histopathological injury scores were significantly increased (P<0.05). By contrast, body weights, liver (kidney) organ coefficient, and renal histopathological injury scores were comparable in the control mice and the mice fed with drinking water containing high levels of a single ion alone or housed at high temperature alone (P>0.05). Furthermore, the renal histopathological injury score showed no significant differences between the fluoride-calcium-sodium ion exposure group and the fluoride-calcium-sodium-bromide ion exposure group (P>0.05). The interaction between bromide ions and fluoride-calcium-sodium ions on renal tissue pathological damage was not statistically significant (P>0.05). Results from the TUNEL assay showed a significant increase in renal cell apoptosis in the fluoride-calcium-sodium ion exposure group (P<0.05).

    Conclusions

    Environmental high levels of mixed fluoride, calcium, and sodium ions in drinking water induce renal pathological damage in mice, which are exacerbated in combination with high temperature environment. High temperature exposure alone does not affect the pathological damage of renal tissue,

     

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