目的:探究慢性氟中毒对心肌的毒性作用及其对JNK介导的凋亡影响。方法:将Wistar大鼠随机分为4组,分别为对照组及不同浓度的氟化钠溶液(50、100、200 mg·L-1 NaF)处理组,各处理组大鼠自由饮用各自浓度的氟化钠溶液,对照组大鼠饮用去离子水。4个月后获得慢性氟中毒大鼠模型,通过HE染色法比较不同浓度NaF对大鼠心肌组织结构的影响,观察心肌组织的损伤情况;使用Western blot法对心肌组织凋亡相关蛋白的表达进行检测,观察NaF对凋亡蛋白表达量的影响,主要包括p-JNK、Bcl-2、Bax和Caspase-3蛋白表达情况。结果:4个月后建立了慢性氟中毒大鼠模型,氟中毒各组大鼠心肌组织出现肌纤维结构紊乱、肌纤维断裂、肌细胞萎缩、肌间隙增宽、横纹消失等;Western blot检测的结果表明,与对照组相比,慢性氟中毒各组大鼠心肌Bcl-2蛋白表达量明显降低(P＜0.05),Bax、Caspase-3和p-JNK的蛋白表达明显上调(P＜0.05)。结论:慢性氟中毒可能通过激活JNK信号通路引起心肌凋亡,细胞凋亡参与了氟对心肌组织的损伤。
Objective: To explore the toxic effect of chronic fluorosis on myocardium and its effect on JNK-mediated apoptosis. Methods: Wistar rats were randomly divided into 4 groups: control group and different concentrations of sodium fluoride solution groups (50, 100, 200 mg·L-1 NaF). The rats were free to drink, and the control group drank deionized water. After 4 months, the rat model of chronic fluorosis was obtained. The effects of different concentrations of NaF on the myocardial tissue structure of rats were compared by HE staining, and the damage of myocardial tissue was observed. The expression of apoptosis-related proteins in myocardial tissue was detected by Western blot, and the effect of NaF on the expression of apoptotic proteins was observed, including p-JNK, Bcl-2, Bax and Caspase-3 protein expression. Results: After 4 months, a rat model of chronic fluorosis was established. The myocardial tissue of rats in each group showed muscle fiber structure disorder, muscle fiber breakage, muscle cell atrophy, muscle gap widening, and disappearance of transverse striations. The results of Western blot showed that compared with the control group, the expression of Bcl-2 protein in myocardium of rats with chronic fluorosis was significantly decreased (P＜0.05), and the expression of Bax, Caspase-3 and p-JNK protein was significantly up-regulated (P＜0.05). Conclusion: Chronic fluorosis may cause myocardial apoptosis by activating JNK signaling pathway, and apoptosis is involved in the damage of fluoride to myocardial tissue.
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