Notch1调控在糖尿病周围神经病变中的意义  

Role of Notch1 in the pathogenesis of diabetic peripheral neuropathy

作　　者：宋宜忻 李懂[2] 陈奇 邵青 梁秋华[2] 孙琳[2] Song Yixin;Li Dong;Chen Qi;Shao Qing;Liang Qiuhua;Sun Lin(Grade 2017 graduate student of Clinical Medical College of Jining Medical College,Jining 272000,China;Department of Endocrinology,Affiliated Hospital of Jining Medical College,Jining 272000,China)

机构地区：[1]济宁医学院临床医学院,山东济宁272000 [2]济宁医学院附属医院内分泌一科,山东济宁272000

出　　处：《中国临床实用医学》2020年第5期54-60,共7页China Clinical Practical Medicine

基　　金：山东省自然科学基金(ZR2017LH024)。

摘　　要：目的探讨Notch1调控在糖尿病周围神经病变(DPN)中的意义。方法选取济南朋悦生物有限公司提供的24只6周龄雄性SD大鼠,无特定病原体级,体质量200~220 g,采用随机数表法将大鼠随机分为正常组、DPN组、DPN+信号通路阻断剂γ-分泌酶抑制剂(3,5-二氟苯乙酰基)-L-丙氨酰基-L-2-苯基甘氨酸叔丁(DAPT)组,每组8只。分别观察比较造模后1、4、8周三组大鼠的一般情况、血糖、体质量、坐骨神经传导速度、足底热痛阈值情况的变化及各组SD大鼠的坐骨神经甲苯胺蓝染色。采用免疫荧光检测DAPT对大鼠坐骨神经Notch1、人第10号染色体缺失的磷酸酶(PTEN)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)表达的影响。结果造模后8周DPN组和DPN+DAPT组大鼠血糖[(22.16±4.77)mmol/L、(17.16±4.43)mmol/L]显著高于正常组大鼠[(6.28±0.51)mmol/L],且DPN+DAPT组血糖水平显著低于同期的DPN组;造模后4、8周,DPN组、DPN+DAPT组大鼠的体质量[(250.00±7.48)g、(250.38±11.02)g,(274.75±9.15)g、(311.50±7.89)g]均显著低于正常组[(363.00±8.98)g、(408.75±16.14)g],且DPN+DAPT组大鼠的体质量高于DPN组;造模后4、8周,DPN组、DPN+DAPT组大鼠坐骨神经传导速度[(25.50±2.56)m/s、(28.13±1.96)m/s,(24.75±1.91)m/s、(32.25±2.44)m/s]显著低于正常组[(38.00±3.70)m/s、(41.25±2.71)m/s],且DPN+DAPT组大鼠坐骨神经传导速度高于DPN组;造模后4、8周,DPN组、DPN+DAPT组大鼠足底热痛阈值[(26.63±3.54)s、(22.50±2.56)s,(28.50±5.10)s、(21.00±3.02)s]显著高于正常组[(12.88±1.13)s、(13.50±2.01)s],且DPN+DAPT组大鼠足底热痛阈值低于DPN组,差异均有统计学意义(P<0.05)。造模后8周DPN组病变髓鞘的比例高于正常组,DPN+DAPT组病变髓鞘的比例低于DPN组;DPN组的Notch1、mTOR、Akt绿色免疫荧光强度强于正常组,DPN+DAPT组的绿色免疫荧光强度弱于DPN组;DPN组的PTEN绿色免疫荧光强度弱于正常组,DPN+DAPT组的绿色免疫荧光强度强于DPNObjective To investigate the role of Notch1 in the pathogenesis of diabetic peripheral neuropathy(DPN).Methods A total of 24 six-week-old male SD rats with body weight of 200~220 g were selected from specefic pathogen free,rats were randomly divided into normal group,DPN group,DPN+(3,5-Difluorophenacetyl)-L-alanyl-S-phenylglycine-2-butyl Ester(DAPT)group,with 8 rats in each group.The changes of general condition,blood glucose,body mass,sciatic nerve conduction velocity,foot sole heat pain threshold and sciatic nerve blue staining of SD rats were observed and compared at 1,4 and 8 weeks after administration.The effects of DAPT on the expression of Notch1 in rats and phosphatase and tensin homolog deleted on chromosome ten(PTEN)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)were examined by immunofluorescence.Results After 8 weeks,the glucose levels of rats in the DPN+DAPT group[(22.16±4.77)mmol/L,(17.16±4.43)mmol/L]were significantly higher than those in the normal group[(6.28±0.51)mmol/L],and the glucose levels in the DPN+DAPT group were significantly lower than those in the DPN+DAPT group.After 4 and 8 weeks,the body weight[(250.00±7.48)g,(250.38±11.02)g,(274.75±9.15)g,(311.50±7.89)g]in DPN group and DPN+DAPT group were significantly lower than that in normal group[(363.00±8.98)g,(408.75±16.14)g],the body weight of DPN+DAPT Group was higher than that of DPN group.After 4 and 8 weeks,the sciatic nerve conduction velocity[(25.50±2.56)m/s,(28.13±1.96)m/s,(24.75±1.91)m/s,(32.25±2.44)m/s]in the DPN group and DPN+DAPT group was significantly lower than that in the normal group[(38.00±3.70)m/s,(41.25±2.71)m/s],and sciatic nerve conduction velocity in the DPN+DAPT group was higher than that in the DPN group.After 4 and 8 weeks,the thermal pain thresholds of the rats in the DPN group and DPN+DAPT group[(26.63±3.54)s,(22.50±2.56)s,(28.50±5.10)s,(21.00±3.02)s]were significantly higher than those in the normal group[(12.88±1.13)s,(13.50±2.01)s],and the thermal pain thresholds of the rats in t

关 键 词：Notch1信号通路 人第10号染色体缺失的磷酸酶 蛋白激酶B 哺乳动物雷帕霉素靶蛋白 糖尿病周围神经病变 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学]