糖络宁通过SIRT1减轻糖尿病小鼠坐骨神经细胞焦亡的机制研究  

Mechanism of Tangluoning for alleviating pyroapoptosis of sciatic nerve cells in diabetic mice by SIRT1

作　　者：吴长江 王晓磊 张晨 辛竞妍 谢文莹 李文慧 卓振南 胡浩 张涛静[2] WU Chang-jiang;WANG Xiao-lei;ZHANG Chen;XIN Jing-yan;XIE Wen-ying;LI Wen-hui;ZHUO Zhen-nan;HU Hao;ZHANG Tao-jing(The Second Clinical Medical College of Bejing University of Chinese Medicine,Beijing 100029,China;Department of Endocrinology,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078)

机构地区：[1]北京中医药大学第二临床医学院,北京100029 [2]北京中医药大学东方医院内分泌科,北京100078

出　　处：《北京中医药》2022年第11期1222-1225,共4页Beijing Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81774223)。

摘　　要：目的 探讨糖络宁通过沉默信息调节因子2相关酶1 (SIRT1)减轻KK-Ay糖尿病小鼠坐骨神经细胞焦亡的机制。方法 选用8周龄SPF级雄性C57BL/6J小鼠10只,普通饲料喂养作为空白对照组;8周龄SPF级雄性KK-Ay小鼠35只,高脂饲料喂养4周,检测小鼠随机血糖≥16.7 mmol/L视为糖尿病小鼠模型造模成功。将造模成功的30只小鼠随机分为模型组、糖络宁低剂量组、糖络宁高剂量组3个组。糖络宁低剂量组按生药10 g/(kg·d)灌胃,糖络宁高剂量组按生药20 g/(kg·d)灌胃,空白对照组和模型组予等体积蒸馏水灌胃,实验期间自由饮食,连续给药12周。采用透射电镜观察坐骨神经细胞形态结构,Western blot检测SIRT1及焦亡相关分子Caspase1、NOD样受体热蛋白结构域相关蛋白3 (NLRP3)、膜穿孔蛋白D (GSDMD)的表达水平。结果 与空白对照组比较,模型组小鼠SIRT1蛋白表达水平显著下调(P<0.05),Caspase1、NLRP3、GSDMD蛋白表达水平升高(P<0.05);与模型组比较,糖络宁高剂量组SIRT1蛋白表达显著升高(P<0.05),Caspase1、NLRP3和GSDMD蛋白表达水平均降低(P<0.05)。结论 糖络宁可以减轻糖尿病周围神经病变小鼠坐骨神经细胞的焦亡,其部分作用机制可能是通过上调SIRT1实现,而高剂量的糖络宁效果更加明显。Objective To investigate the mechanism of Tangluoning for alleviating pyrodeath of sciatic nerve cells in KK-Ay diabetic mice by SIRT1. Methods Ten SPF male C57BL/6J mice aged 8 weeks with ordinary feed were selected as blank control group and 30 SPF male KK-Ay mice aged 8 weeks were fed with high fat diet for 4 weeks. Random blood glucose ≥16. 7mmol/L was detected as diabetic mouse model was successfully established. The successfully modeled mice were randomly divided into three groups:model group,low-dose Tangluoning group and high-dose Tangluoning group. The low-dose Tangluoning group was given intragastric administration of crude drug 10g/(kg·d), the high-dose Tangluoning group was given intragastric administration of crude drug 20g/(kg·d),the blank control group and the model group were given intragastric administration of equal volume distilled water, free diet during the experiment, continuous administration for 12 weeks. The morphological structure of sciatic nerve cells was observed by transmission electron microscopy, and the expression levels of SIRT1 and scorched-death related molecules(Caspase1, NLRP3, GSDMD) were detected by Western blot. Results Compared with the blank control group, the expression level of SIRT1 protein in model group was significantly down-regulated(P<0. 05), the protein expression levels of Caspase1,NLRP3 and GSDMD increased(P<0. 05);compared with the model group, SIRT1 protein expression in Tangluoning high-dose group was significantly increased(P<0. 05), Caspase1, NLRP3 and GSDMD protein expression levels were decreased(P<0. 05). Conclusion Tangluoning can reduce scorch death of sciatic nerve cells in DPN mice,and part of its mechanism may be realized through up-regulation of SIRT1, and the effect of high-dose Tangluoning is more obvious.

关 键 词：糖络宁 SIRT1 坐骨神经 细胞焦亡 小鼠 

分 类 号：R285.5[医药卫生—中药学]