目的: 探究长期氟暴露对大鼠心肌半胱氨酸天冬氨酸蛋白酶-1(Cysteinyl aspartate specific proteinase,caspase-1)和肿瘤坏死因子(Tumor necrosis factor-α,TNF-α)表达的影响。方法: 将Wistar大鼠作为实验对象,采用随机数字法将其随机分为4组,即空白对照组、低剂量染氟组、中剂量染氟组和高剂量染氟组。空白对照组大鼠饮用去离子水,染氟组大鼠饮用不同剂量的氟化钠去离子水,所选浓度为50、100、200 mg/L,各组自由进食饮水,喂养7个月,制备长期氟暴露动物模型。采用免疫组织化学染色法检测长期氟暴露的大鼠心肌caspase-1和TNF-α表达情况。结果: 染毒7个月后,与空白对照组相比,不同剂量染氟组大鼠呈现不同程度的氟斑牙,且氟斑牙程度与染氟剂量呈剂量依赖性;免疫组织化学染色结果显示,与空白对照组相比,不同剂量染氟组大鼠心肌细胞caspase-1和TNF-α表达水平增加,且呈剂量依赖性(P＜0.05)。结论: 长期氟暴露可能会通过依赖caspase-1诱导大鼠心肌细胞产生大量炎症因子,从而导致心肌细胞损伤。
Objective: To investigate the effect of long-term fluorine exposure on the expression of cysteinyl aspartate specific proteinase (caspase-1) and tumor necrosis factor-α (TNF-α) in rat myocardium. Methods: Wistar rats were randomly divided into the control group, the low-dose fluoride (50 mg/L) group, the middle-dose fluoride (100 mg/L) group and the high-dose fluoride (200 mg/L) group. The rats in the control group were fed with deionized water, and the rats in the fluoride groups were given deionized water containing different doses of sodium fluoride (NaF). Rats in each group were fed freely for 7 months to make an animal model of long-term fluoride exposure. Immunohistochemical staining was used to detect the expression level of myocardial Caspase-1 and TNF-α in long-term fluorine-exposed rats. Results: Compared with the rats in the control group, rats in the fluoride groups showed different degrees of dental fluorosis (DF), and the degree of fluorosis was dose - dependent with the dose of fluoride. The results of immunohistochemical staining showed that the expression levels of Caspase-1 and TNF-α in cardiomyocytes of rats stained with fluoride were increased (P＜0.05) and dose-dependent compared with rats in the control group. Conclusion: Long-term fluorine exposure may induce massive inflammatory factors in rat cardiomyocytes and cause cardiomyocyte damage by regulating caspase-1 level.
[1] James P, Harding M, Beecher T, et al. Impact of reducing water fluoride on dental caries and fluorosis[J]. J Dent Res, 2021, 100(5): 507-514.
[2] Solanki YS, Agarwal M, Maheshwari K, et al. Removal of fluoride from water by using a coagulant (inorganic polymeric coagulant)[J]. Environ Sci Pollut Res Int, 2021, 28(4): 3897-3905.
[3] Caglayan C, Kandemir FM, Darendelioĝlu E, et al. Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms[J]. Life Sci, 2021, 281: 119730.
[4] Wang HW, Zhao WP, Liu J, et al. ATP5J and ATP5H proactive expression correlates with cardiomyocyte mitochondrial dysfunction induced by fluoride[J]. Biol Trace Elem Res, 2017, 180(1): 63-69.
[5] Varşlι B, Darendelioĝlu E, Caglayan C, et al. Hesperidin attenuates oxidative stress, inflammation, apoptosis, and cardiac dysfunction in sodium fluoride-induced cardiotoxicity in rats[J]. Cardiovasc Toxicol, 2022, 22(8): 727-735.
[6] Li MY, Wang JM, Wu PH, et al. Self-recovery study of the adverse effects of fluoride on small intestine: involvement of pyroptosis induced inflammation[J]. Sci Total Environ, 2020, 742: 140533.
[7] 徐薇, 曹丽婷, 石瑞丽, 等. 氟化钠暴露诱导的心肌细胞凋亡中死亡受体通路的作用[J]. 中国药理学通报, 2021, 37(12): 1715-1720.
[8] 吴云飞, 王茂华, 陈庄. 不同浓度氟化物对大鼠心肌细胞的毒性作用及细胞凋亡机制研究[J]. 中国地方病防治杂志, 2016, 31(6): 619-620.
[9] Yan XY, Dong NS, Hao XH, et al. Comparative transcriptomics reveals the role of the toll-like receptor signaling pathway in fluoride-induced cardiotoxicity[J]. J Agric Food Chem, 2019, 67(17): 5033-5042.
[10] 马宝慧, 潘桂兰, 陈晓东, 等. 慢性氟中毒对大鼠血清氧化应激反应的影响[J]. 中国现代医药杂志, 2012, 14(9): 5-6.
[11] Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, et al. Cellular death, reactive oxygen species (ROS) and diabetic complications[J]. Cell Death Dis, 2018, 9(2): 119.
[12] 裴月皓, 唐学弘, 程国杰. 冠心病患者介入治疗前后血清中TNF-α、IL-1β和caspase-1水平变化及意义[J]. 中国循证心血管医学杂志, 2021, 13(7): 815-818.
[13] Panneerselvam L, Raghunath A, Sundarraj K, et al. Acute fluoride exposure alters myocardial redox and inflammatory markers in rats[J]. Mol Biol Rep, 2019, 46(6): 6155-6164.
[14] Syed FM, Hahn HS, Odley A, et al. Proapoptotic effects of caspase-1/interleukin-converting enzyme dominate in myocardial ischemia[J]. Circ Res, 2005, 96(10): 1103-1109.
[15] Shi MQ, Su FF, Dong ZW, et al. TRIM16 exerts protective function on myocardial ischemia/reperfusion injury through reducing pyroptosis and inflammation via NLRP3 signaling[J]. Biochem Biophys Res Commun, 2022, 632: 122-128.
[16] Luo BB, Huang F, Liu YL, et al. NLRP3 inflammasome as a molecular marker in diabetic cardiomyopathy[J]. Front Physiol, 2017, 8: 519.
[17] Yue RC, Zheng ZY, Luo Y, et al. NLRP3-mediated pyroptosis aggravates pressure overload-induced cardiac hypertrophy, fibrosis, and dysfunction in mice: cardioprotective role of irisin[J]. Cell Death Discov, 2021, 7(1): 50.
[18] 吕展, 李行, 李戈锐, 等. 3’,4’-二羟基黄酮醇通过抑制caspase1的活化减轻血管紧张素Ⅱ诱导的心肌肥厚[J]. 中华生物医学工程杂志, 2021, (2): 117-126.
[19] Zheng YD, Xu L, Dong ND, et al. NLRP3 inflammasome: the rising star in cardiovascular diseases[J]. Front Cardiovasc Med, 2022, 9: 927061.
