摘要
55只SD大鼠随机分为对照组、模型组、解毒通络调肝方组以及盐酸二甲双胍组,其中45只采用高糖高脂联合腹腔注射链脲佐菌素的方式诱导2型糖尿病模型,给药4周后麻醉处死取样。Morris水迷宫试验法测试大鼠空间学习能力,血生化检测空腹血糖、空腹血清胰岛素,HE染色法观察SD大鼠海马组织病理变化,免疫组织化学法检测BDNF蛋白表达,Western blot法检测CREB、GLUT4、PI3K、AKT、GSK3β蛋白表达。结果提示:与对照组相比,模型组空腹血糖、空腹血清胰岛素显著升高(P<0.01),水迷宫试验相关指标提示大鼠空间学习能力降低(P<0.01),BDNF蛋白阳性表达明显降低(P<0.01),CREB、GLUT4、PI3K、AKT蛋白表达也均呈现出明显降低(P<0.001,P<0.01),GSK3β蛋白表达升高(P<0.001);与模型组相比,给药组大鼠空腹血糖、空腹血清胰岛素均明显下降(P<0.01),水迷宫试验相关指标提示大鼠空间学习能力提升(P<0.01),BNDF阳性表达增加(P<0.01),CREB、GLUT4、PI3K、AKT蛋白表达均显著增加(P<0.001,P<0.01,P<0.05),GSK3β蛋白表达下降(P<0.001)。结果表明,解毒通络调肝方能够提高2型糖尿病认知障碍大鼠的认知能力,其作用机制可能是通过调控海马组织中BDNF、CREB、GLUT4蛋白表达,影响PI3K/AKT/GSK-3β信号通路实现的。
The aim of this study was to investigate the effect of Jiedu Tongluo Tiaogan decoction(JTTD)on PI3K/AKT/GSK3βsignaling pathway in hippocampal tissues of SD mice model of type 2 diabetes mellitus-associated cognitive dysfunction.Fifty-five male SD mice were randomly divided into control group,model group,JTTD group and metformin hydrochloride group.Among them,45 rats were induced into type 2 diabetes models by high glucose and high fat combined with intraperitoneal injection of streptozotocin and were anesthetized and killed for sampling 4 weeks after administration.The expression of BDNF,CREB,GLUT4,PI3K,AKT and GSK3βwere detected by immunohistochemistry and Western blot,the hippocampal histopathological change was detected by HE staining,fasting blood glucose and fasting serum insulin by was detected by blood biochemistry,and spatial learning ability was detected by Morris water maze test.The results showed that compared with control group,the levels of blood biochemical in model group were obviously improved(P<0.01),and indicators related to water maze test suggested that the spatial learning ability of mice was reduced(P<0.01).The expression of BDNF CREB,GLUT4,PI3K,AKT,and GSK3βprotein all showed a decreasing state(P<0.01).Compared with model group,we found that the levels of blood biochemical indexes in administered groups were apparently decreased(P<0.01),and the indexes related to water maze test suggested that the spatial learning ability of mice improved(P<0.01),the positive expression of BNDF showed a significant increase(P<0.01),and expression of CREB,GLUT4,PI3K,AKT,GSK3βprotein showed a significant increase(P<0.01).The results suggested that JTTD could improve cognitive ability of SD mice with type2diabetes mellitus cognitive impairment,and its mechanism of action may be achieved by regulating the expression of BDNF,CREB,GLUT4protein in hippocampal tissue and affecting PI3K/AKT/GSK-3βsignaling pathway.
作者
苏婧
崔镇海
金美英
SU Jing;CUI Zhenhai;JIN Meiying(Changchun University of Chinese Medicine,Changchun 130021,China;The Third Affiliated Clinical Hospital,Changchun University of Chinese Medicine,Changchun 130117,China)
出处
《中国兽医学报》
CAS
CSCD
北大核心
2023年第11期2347-2353,共7页
Chinese Journal of Veterinary Science
基金
吉林省科技厅资助项目(20210101218JC)。
关键词
2型糖尿病
认知障碍
解毒通络调肝方
PI3K/AKT/GSK3β通路
胰岛素抵抗
毒损脑络
type 2 diabetes mellitus cognitive impairment
Jiedu Tongluo Tiaogan decoction
PI3K/AKT/GSK3βpathway
insulin resistance
mechanism of brain collateral damage by internal toxin
