氟对链脲佐菌素诱导的1型糖尿病大鼠的毒性作用及其对糖尿病进程的影响

目的:观察给予氟(F-)后糖尿病大鼠切牙的病理性改变以及氟对糖尿病大鼠生理指标的影响,阐明氟在糖尿病进程中的作用。方法:雄性Wistar大鼠54只,按体质量平均分成对照组、10mg·kg-1·d-1氟组和20mg·kg-1·d-1氟组,每组18只;按相应剂量灌胃给氟4周后,每组随机选12只,一次性腹腔注射50mg·kg-1体质量剂量的STZ,复制大鼠1型糖尿病模型(分别为STZ对照组、10 mg F-+STZ组和20mg F-+STZ组),与每组剩余6只大鼠(分别为正常对照组、10mg F-组和20mg F-组)同时继续给氟饲养4周(STZ对照组和正常对照组不给氟)。实验周期内用电子天平每周测量1次大鼠体质量;便携式血糖仪每周测量1次大鼠血糖;利用数码相机对大鼠牙齿的渐进性变化进行拍照;实验结束前采用腹腔注射胰岛素进行糖耐量实验(ITT),观察大鼠胰岛素的敏感性。结果:10mg F-和20mg F-组大鼠切牙面逐渐由棕黄色转向淡黄色,着色不匀,部分区域有白色不透光改变,牙面粗糙,呈现氟斑牙病变;与正常对照组比较,单纯氟中毒大鼠体质量无变化。腹腔注射STZ后的3组大鼠体质量均呈下降的趋势,20mg F-组降幅最大,但与正常对照组比较差异无统计学意义(P>0.05);腹腔注射STZ后各组大鼠血糖明显上升,与正常对照组比较差异有统计学意义(P<0.05),20mg F-+STZ组大鼠血糖水平最高,但与STZ对照组比较差异无统计学意义(P>0.05)。ITT结果,20mg F-组大鼠腹腔注射胰岛素0.5、1和2h时血糖水平显著高于正常对照组(P<0.05),而10mg F-组大鼠血糖水平虽高于正常对照组,但差异无统计学意义(P>0.05)。结论:高剂量氟可短期内引起大鼠氟斑牙,并加剧糖尿病引起的大鼠体质量下降和血糖升高,明显降低大鼠胰岛素敏感性。

Toxicity effect of fluoride on rats with type 1diabetes mellitus induced by streptozotocin and its influence in process of diabetes mellitus

Objective To observe the influence of fluoride in the pathological changes of incisor and the changes ofphysiological indicators of the rats with type 1diabetes mellitus,and to clarify the effect of fluoride on process of diabetes mellitus.Methods 54male Wistar rats were divided into control group(n=18),10mg·kg-1·d-1 Fgroup(10mg F-)(n=18)and 20mg·kg-1·d-1 F-group(20mg F-)(n=18).Fluoride was fed by gavage, 1month later 12rats in each group were selected and treated with single intraperitoneal injection of 50mg·kg-1 STZ to induce type 1diabetes mellitus(used as STZ control group,10mg F-+STZ group,and 20mg F-+STZ group),then the remaining 6rats were fed with fluoride for 4weeks(used as normal control group,10mg Fgroup,and 20mg F-group).In the experimental period,the changes of blood glucose were measured by glucose meter weekly,and the photograph was taken to follow teeth progressive changes.Before the end of experiment, intraperitoneal injection of insulin was performed to test the insulin sensitivity of the rats by insulin tolerance test(ITT).Results The rat dental face in 10mgF-and 20mg F-groups gradually shifted from yellow to pale and turned to rough,uneven coloring,part of the teeth with white opaque changes,showing dental fluorosis alteration.Compared with normal control group,the rats in simple fluoride poisoning group had no change in weight,but after intraperitoneal injection of STZ,the weights of the rats in three groups showed downward trend, especially in 20mg F-group,but there was no significant difference(P>0.05);after STZ induction the blood glucose levels were increased significantly(P<0.05)compared with normal control group;and the blood glucose level in 20mg F-+STZ group had obviously change,but there was no significant difference(P>0.05)compared with STZ control group.The ITT results showed that the glucose levels in 20 mg F-group were significantly higher than those in normal control group(P<0.05)at 0.5,1and 2h,while the glucose level in 10mg F-group was elevated,but the difference was not statistically significant(P>0.05).Conclusion High dose of fluoride can cause short-term dental fluorosis,aggravate the diabetes-induced body weight loss and blood sugar increasing,and decrease the insulin sensitivity in rats.