PFOS暴露促胰岛β细胞损伤及功能下降的实验研究

Experimental study on isletβcell damage and functional decline induced by perfluorooctane sulfonate exposure

目的 观察全氟辛烷磺酰基化合物(PFOS)暴露对2型糖尿病小鼠胰岛β细胞结构和功能的影响。方法 通过高脂喂饲建立2型糖尿病小鼠模型。90只6周龄SPF级雄性C57BL/6小鼠随机分为对照组、低剂量组和高剂量组,以灌胃方式,分别对小鼠进行0、1、5 mg/kg剂量浓度的PFOS染毒4周后,对小鼠进行葡萄糖耐量检测,分析小鼠血清胰岛素水平变化,评估PFOS染毒对小鼠胰岛功能和葡萄糖代谢的影响;采用HE染色和透射电镜观察小鼠胰腺组织的病理学改变;采用免疫荧光技术分析PFOS染毒对小鼠胰腺组织中胰岛素蛋白表达的影响。结果 PFOS染毒28 d后,高脂喂饲小鼠体重出现反常的下降,胰腺重量和脏器指数下降,空腹血糖升高,葡萄糖耐量出现异常,血清胰岛素水平减低;HE染色和透射电镜结果显示PFOS染毒导致胰岛形态严重受损,细胞核小而致密,细胞间隙不明显;免疫荧光结果显示胰岛素蛋白荧光信号减弱,细胞分泌胰岛素蛋白表达水平下降。结论 PFOS染毒可加剧高脂诱导的胰岛β细胞损伤,促进2型糖尿病进程;PFOS染毒单独作用并不会引起典型的2型糖尿病,其主要作为风险因素加速其他致病因素介导的2型糖尿病进程。

Objective To observe the effects of perfluorooctane sulfonate(PFOS)exposure on the structure and function of isletβcells in type 2 diabetes mellitus in mice.Methods A mouse model of type 2 diabetes mellitus was established using a high-fat diet.Ninety SPF male C57BL/6 mice(6-week-old)were randomly divided into control group,low-dose PFOS group,and high-dose PFOS group to receive intragastric administration of PFOS at concentrations of 0,1,and 5 mg/kg,respectively,for a total of four weeks.Af-ter PFOS exposure,the effects of PFOS exposure on islet function and glucose metabolism in mice were evaluated through glucose toler-ance testing and measuring the changes in serum insulin levels;pancreatic tissue pathological changes were examined with HE staining and transmission electron microscopy;and the changes in insulin protein expression in the pancreatic tissue were determined by immu-nofluorescence assay.Results After 28 days of exposure to PFOS,the mice with a high-fat diet showed an abnormally decreased body weight,reduced pancreatic weight and pancreatic index,increased fasting blood glucose level,abnormal glucose tolerance,and de-creased serum insulin level.HE staining and transmission electron microscopy results showed that PFOS exposure resulted in severe damage to islet morphology,with small and dense nuclei and blurred intercellular spaces.Immunofluorescence results showed attenua-ted fluorescence signal of insulin proteins,indicating a reduction in the expression of insulin proteins in islet cells.Conclusion PFOS exposure can aggravate pancreaticβcell damage induced by a high-fat diet to promote the development of type 2 diabetes.PFOS expo-sure alone cannot cause typical type 2 diabetes,which mainly serves as a risk factor to accelerate the development of type 2 diabetes mediated by other pathogenic factors.