Full-Text Search:
Home|About CNKI|User Service|中文
Add to Favorite Get Latest Update

Effect and possible mechanism of dihydroartemisinin on glucolipid metabolism and hippocampal neurons in diabetic rats complicated with depression

CHEN Zi-wen;YANG Chun-hua;QUAN Rui;WANG Chang-qing;Western Pharmacy,the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture;Traditional Chinese Medicine Pharmacy,the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture;  
Objective To investigate the effect and possible mechanism of action of dihydroartemisinin(DHA) on glucolipid metabolism and hippocampal neurons in diabetic rats complicated with depression.Methods Thirty-five rats were randomly divided into control group, chronic unpredictable mild stress(CUMS) group, CUMS+25 mg/kg DHA group, CUMS+50 mg/kg DHA group and CUMS+100 mg/kg DHA group, with seven rats in each group. Except for the control group, rat models of diabetes complicated with depression were established in the remaining groups. After successful modeling, rats in various DHA intervention groups were given intraperitoneal injections of corresponding dosages of DHA, and the control and CUMS groups were intraperitoneally injected with the same amount of normal saline. After four weeks of the intervention, the levels of fasting blood glucose, serum insulin, blood lipid, serum 5-hydroxytryptamine(5-HT), and 5-hydroxyindoleacetic acid(5-HIAA) were detected in each group, and the histopathological changes and apoptosis in hippocampal tissues were observed; besides, the expression levels of glutamate transporter 1(GLT-1), brain-derived neurotrophic factor(BDNF), phosphorylated adenosine 5′-monophosphate-activated protein kinase α1 subunit(p-AMPKα1), peroxisome proliferator γ activated receptor coactivator 1α(PPARGC1 A), and glucose transporter 4(GLUT4) proteins were detected. Results(1)Compared with the control group, rats in the CUMS group exhibited a higher level of fasting blood glucose, elevated serum levels of insulin, total cholesterol, triacylglycerol and LDL-C, a lower serum HDL-C level, a decreased hippocampal p-AMPKα1/adenosine 5′-monophosphate-activated protein kinase α1 subunit(AMPKα1) ratio, and down-regulated expression of PPARGC1 A and GLUT4 proteins in hippocampal tissues(all P0.05). Compared with the CUMS group, rats in the CUMS+50 mg/kg DHA and CUMS+100 mg/kg DHA groups yielded lower levels of fasting blood glucose, decreased serum levels of insulin, total cholesterol, triacylglycerol, and LDL-C, higher serum HDL-C levels, increased p-AMPKα1/AMPKα1 ratios, and up-regulated expression of PPARGC1 A and GLUT4 proteins(all P0.05).(2)Compared with the control group, rats in the CUMS group showed an increase in the number of apoptotic cells in brain tissues(P0.05), a decrease in the number of hippocampal neurons and some with pyknosis and increased staining degree, lower serum levels of 5-HT and 5-HIAA, down-regulated expression of GLT-1 and BDNF proteins in hippocampal tissues(all P0.05); furthermore, compared with the CUMS group, rats in the CUMS+50 mg/kg DHA and CUMS+100 mg/kg DHA groups showed decline in the number of apoptotic cells in brain tissues(P0.05), an increase in the number of hippocampal neurons, most of which were intact in structure, elevated serum levels of 5-HT and 5-HIAA, and up-regulated expression of GLT-1 and BDNF proteins in hippocampal tissues(all P0.05). Conclusion DHA can improve glucolipid metabolism disorder and insulin resistance in diabetic rats complicated with depression via regulating the proteins expression of metabolism-related pathways; besides, DHA can up-regulate the level of monoamine neurotransmitters as well as the expression of GLT-1 and BDNF proteins, suppress hippocampal neuron apoptosis and ameliorate nerve injury, thus hampering the progression of depression in rats.
Download(CAJ format) Download(PDF format)
CAJViewer7.0 supports all the CNKI file formats; AdobeReader only supports the PDF format.
©CNKI All Rights Reserved