摘要
目的探讨消渴方治疗2型糖尿病的可能作用机制。方法采用高脂高糖饲料联合2%链脲佐菌素-柠檬酸缓冲液35mg/kg腹腔注射建立2型糖尿病大鼠模型,造模成功40只大鼠随机分为模型组、抑制剂组、消渴方组、消渴方+抑制剂组,每组10只,另取10只SD大鼠作为正常组。造模后消渴方组大鼠予消渴方17g/(kg·d)灌胃,抑制剂组予VIVIT 0.5mg/(kg·d)尾静脉注射,消渴方+抑制剂组予消渴方水煎剂灌胃联合VIVIT尾静脉注射,模型组及正常组给予1.9 ml生理盐水灌胃。5周后检测空腹血糖(FBG)、空腹胰岛素(FINS)、糖化血清蛋白(GSP)水平及胰腺组织钙离子(Ca^(2+))、钙调磷酸酶(CaN)水平;HE染色观察胰岛病理形态学改变;检测胰腺组织胰岛素及活化T细胞核因子c1(NFATc1)蛋白表达水平及神经元素3(Ngn3)和胰腺十二指肠同源盒因子1(PDX-1)mRNA表达。结果与正常组比较,模型组FBG、GSP水平升高,FINS、CaN、Ca^(2+)、NFATc1、Ngn3 mRNA、PDX-1 mRNA表达均降低(P<0.01),HE染色显示胰岛内细胞数量明显减少,形状不规则,间质增多,部分胰岛组织结构甚至完全萎缩、崩解。与模型组比较,消渴方组各指标均明显改善(P<0.01),HE染色显示胰岛数量明显增多,胰岛呈完整团块状分布,且胰岛内细胞质较丰富。与消渴方组比较,消渴方+抑制剂组FBG、GSP升高,FINS、CaN、Ca^(2+)、NFATc1、Ngn3 mRNA、PDX-1 mRNA表达降低(P<0.05或P<0.01)。结论消渴方可调节血糖、保护胰岛β细胞,其作用机制可能与调节胰腺组织Ca^(2+)/CaN/NFAT信号通路,提高β细胞再生相关转录因子表达有关。
Objective To explore the possible mechanism of Xiaoke Formula(消渴方)for type 2 diabetes mellitus(T2 DM).Methods High-fat and high-sugar feed combined with intraperitoneal injection of 35 mg/kg 2%streptozotocin-citrate buffer were used to establish the T2 DM rat model.Forty successfully modeled rats were randomly divided into model group,inhibitor group,Xiaoke Formula group,Xiaoke Formula plus inhibitor group(combination group),with 10 rats in each group;and another 10 SD rats were set as the normal group.After modeling,rats in the Xiaoke Formula group were given 17 g/(kg·d)Xiaoke Formula by gavage;the inhibitor group was given tail vein injection of 0.5 mg/(kg·d)VIVIT peptide;the combination group received both Xiaoke Formula and VIVIT with the same dose and administration way as other groups;the model group and the normal group were administered with 1.9 ml normal saline by gavage.Five weeks later,levels of fasting blood glucose(FBG),fasting insulin(FINS),glycosylated serum protein(GSP),calcium ion(Ca^(2+))and calcineurin(CaN)in the pancreatic tissue were detected;HE staining was used to observe the pathological changes of pancreatic islets;the protein expression of insulin and nuclear factor of activated T cell c1(NFATc1)in the pancreatic tissue,as well as the mRNA expression of neurogenin 3(Ngn3)and pancreaticoduodenal homeobox factor 1(PDX-1)were detected.Results Compared to those of the normal group,the FBG and GSP levels of the model group significantly increased,and the expressions of FINS,CaN,Ca^(2+),NFATc1,Ngn3 mRNA and PDX-1 mRNA were all decreased(P<0.01).HE staining showed that the cells number of the pancreatic islets was significantly reduced,the shape was irregular,and the interstitium increased;certain islet tissue structures was even completely shrinked and disintegrated.Compared to the model group,Xiaoke Formula group showed better effects on all the outcome measurements(P<0.01).HE staining showed that the number of islets increased significantly,and were distributed in complete clumps wit
作者
陈学麟
杨巧玉
胡剑卓
CHEN Xuelin;YANG Qiaoyu;HU Jianzhuo(Hunan University of Chinese Medicine,Changsha,410208;Third People’s Hospital of Dongguan City,Guangdong;The Second Affiliated Hospital of Hunan University of Chinese Medicine)
出处
《中医杂志》
CSCD
北大核心
2021年第17期1526-1532,共7页
Journal of Traditional Chinese Medicine
基金
湖南省自然科学基金(2018JJ6037)
第六批全国老中医药专家学术经验继承培训项目(国中医药人教发[2017]125号)
湖南中医药大学研究生科研创新课题(2018CX48)。
