基于限制性立方样条探讨BDE-153对C57BL/6小鼠胰岛形态及功能的影响  

Discussion on the effect of BDE-153 on islet morphology and function in C57BL/6 mice based on restriction cubic spline

作　　者：王梦林 李美艳 王嘉穗 姜淑瑞 祖尼热·吐尔逊 刘早玲 WANG Meng-lin;LI Mei-yan;WANG Jia-sui;JIANG Shu-rui;ZUNIRE·Tuerxun;LIU Zao-ling(School of Public Health,Xinjiang Medical University,Urumqi Xinjiang 830011,China;Xinjiang Uygur Autonomous Region People's Hospital,Urumqi Xinjiang 830011,China)

机构地区：[1]新疆医科大学公共卫生学院流行病与卫生统计学教研室,新疆乌鲁木齐830011 [2]新疆维吾尔自治区人民医院,新疆乌鲁木齐830011

出　　处：《毒理学杂志》2023年第1期18-23,30,共7页Journal of Toxicology

基　　金：国家自然科学基金(8216120090,81760596)。

摘　　要：目的 探讨2,2′,4,4′,5,5′-六溴联苯醚(2,2′,4,4′,5,5′-Hexabromodiphenyl ether, BDE-153)暴露对胰岛形态及功能的影响。方法 将36只C57BL/6小鼠分为对照组及不同BDE-153剂量组进行染毒,观察其生长发育情况,行腹腔注射葡萄糖耐量实验及免疫组化形态和量化分析,以评估BDE-153对C57BL/6小鼠胰岛形态及功能的影响。建立剂量—反应关系限制性立方样条模型并作图,构建回归模型,分析BDE-153暴露水平与胰岛功能的关系。结果 染毒期间,各组小鼠体重差异无统计学意义。但BDE-153染毒高剂量组和较高剂量组胰腺重量和胰腺脏器系数均高于对照组(F=7.391,F=7.392,P<0.05,P<0.05)。胰腺组织免疫组化分析显示,与对照组相比,随着BDE-153染毒剂量的增加,小鼠胰岛数量有所增多,胰岛面积稍有增大,形态略不规则。BDE-153染毒高剂量组、较高剂量组、中剂量组和低剂量组胰岛素染色阳性率均高于对照组,差异有统计学意义(F=91.636,P<0.001),且随着BDE-153染毒剂量的增加,胰岛素染色阳性率呈上升趋势。糖耐量实验发现,各组小鼠空腹血糖和胰岛素差异无统计学意义(P>0.05)。腹腔注射葡萄糖后,各组小鼠血糖均有所升高,30 min时染毒最高剂量组和低剂量组血糖明显低于对照组(F=5.184,P<0.05),60和120 min时各组血糖之间差异无统计学意义(P>0.05)。限制性立方样条模型分析显示,BDE-153暴露水平与小鼠30 min血糖的关联强度呈弱非线性的“∪”形剂量—反应关系;BDE-153暴露水平与小鼠胰岛素的关联强度呈微弱的非线性的“∪”形剂量—反应关系;BDE-153暴露水平与小鼠脏器系数的关联强度呈弱对数(Log)曲线形剂量—反应关系;BDE-153暴露水平与胰岛素阳性染色率的关联强度呈非线性的分段剂量—反应关系(非线性检验,均P<0.05),分段回归方程为:(1)当X≤67.7时,Y=0.035X+3.63;(2)当X> 67.7时,Y=0.007 9X+5.45。X为BDE-153暴露剂量(mg/kObjective To investigate the effects of 2,2′, 4,4′, 5,5′-hexabromodiphenyl ether(BDE-153) exposure on pancreatic islet morphology and function in mice. Methods Thirty-six C57BL/6 mice were divided into control group and different BDE-153 dose groups. The growth and development of mice were observed. Glucose tolerance test and immunohistochemical morphology and quantitative analysis were performed to evaluate the effect of BDE-153 on islet morphology and function in C57BL/6 mice.The restricted cubic spline model of dose-response relationship was established and plotted, and the regression model was constructed to analyze the relationship between BDE-153 exposure level and islet function. Results During the exposure period, there was no significant difference in body weight among the groups. The weight and organ coefficient of pancreas in the high dose group and the high dose group were higher than those in the control group(F=7.391,F=7.392,P<0.05,P<0.05). Immunohistochemical analysis of pancreatic tissue showed that compared with the control group, with the increase of BDE-153 exposure dose, the number of islets in mice increased, the area of islets increased slightly, and the shape was slightly irregular. Statistical analysis showed that the positive rate of insulin staining in the highest dose, high dose, medium dose and low dose groups of BDE-153 treatment was higher than that in the control group(F=91.636, P<0.001) and the positive rate of insulin staining increased with the increase in BDE-153 exposure dose. Glucose tolerance test showed that there was no significant difference in fasting blood glucose and insulin in each group(P>0.05). After intraperitoneal injection of glucose, the blood glucose of mice in each group increased, and the blood glucose of the highest dose group and the low dose group was significantly lower than that of the control group at 30 min(P<0.05). There was no significant difference in blood glucose between the groups at 60 and 120 min(P>0.05). The restricted cubic spline analys

关 键 词：六溴联苯醚 胰岛Β细胞 高胰岛素血症 限制性立方样条 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]