Research on the Mechanism of Rosiglitazone in Improving Cognitive Impairment in Senile Diabetic Rats_West China Medical Journal

Authors：

 LIJun ¹ , LIUFei ² , SUNQian-qian ¹ , WANGShuang ¹ ,  XIANGBing ³

1. Geriatric Medical Center, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Department of Nephrology, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Department of Hematology;West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

XIANGBing, Email: xiang7199@hotmail.com

Keywords：

Senile diabetes; Rosiglitazone; Cognitive impairment; C reactive protein; Nuclear factor-κB

DOI：

10.7507/1002-0179.20140504

Video：

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Objective To observe the effect of rosiglitazone on cognitive function, serum high sensitive C reactive protein (hs-CRP) and expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in hippocampal tissues of senile diabetic rats. Methods Thirty aged Wistar rats (20-22 months) were randomly divided into normal control group (n=6), diabetic model group (n=12), and rosiglitazone treatment group (n=12). Streptozotocin-induced diabetic rat model was established. In the rosiglitazone treatment group, the rats were treated with rosiglitazone 4mg/kg/d for 8 weeks. The cognitive function of rats was evaluated with the Morris water maze test. Serum hs-CRP was detected by ELISA. The expression of NF-κB in hippocampal tissues was detected by western blot and IL-6 and TNF-α by Real-time PCR. Results The Morris water maze test showed that escape latency was longer in the rosiglitazone treatment group and the diabetic model group than that in the control group (P<0. 05). Compared with the diabetic model group, the rosiglitazone treatment group showed a significant decrease in the average time of escape latencies (P<0.05), and an increased percentage of time spent in the central area and the more times navigating the original platform position (P<0.05). Serum hs-CRP and the expression of NF-κB, IL-6 and TNF-α in the rosiglitazone treatment group and the diabetic model group was significantly higher than those in the control group (P<0.01). Compared with the diabetic model group, serum hs-CRP and the expression of NF-κB, IL-6 and TNF-α in the rosiglitazone treatment group was decreased (P<0.05). Conclusion Cognitive impairment in senile diabetic rats is associated with serum hs-CRP. The cognitive function can be improved with rosiglitazone treatment. The protective mechanisms may be related to the decrease of serum hs-CRP, inhibition of NF-κB signal and down-regulation of the expression of IL-6 and TNF-α in hippocampal tissues.

Citation： LIJun, LIUFei, SUNQian-qian, WANGShuang, XIANGBing. Research on the Mechanism of Rosiglitazone in Improving Cognitive Impairment in Senile Diabetic Rats. West China Medical Journal, 2014, 29(9): 1642-1646. doi: 10.7507/1002-0179.20140504 Copy

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16.	刘尊敬,杨期东,刘运海,等.过氧化小体增殖剂激活型受体 γ激活剂对缺血再灌注脑组织的保护作用及炎性机制分析[J].国际神经病学神经外科学杂志,2007,34(2):121-124.
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19.	张亭亭,刘丽萍,姜荔莹,等.罗格列酮改善链脲霉素诱导的糖尿病小鼠认知障碍及机制研究[J].神经药理学报,2011,1(2):1-6.
20.	谢英才,周和超,黄贵心.罗格列酮对胰岛素抵抗大鼠血清 C反应蛋白表达水平的抑制作用[J].中国现代医学杂志,2008,18(18):2622-2624.
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22.	Abdin AA,Baalash AA,Hamooda HE.Effects of rosiglitazone and aspirin on experimental model of induced type 2 diabetes in rats:focus on insulin resistance and inflammatory markers[J].J Diabetes Complications,2010,24(3):168-178.

1. Kravitz BA,Corrada MM,Kawas CH.Elevated C-reactive protein levels are associated with prevalent dementia in the oldest-old[J].Alzheimers Dement,2009,5(4):318-323.
2. Schmidt R,Schmidt H,Curb JD,et al.Early inflammation and dementia:a 25-year follow-up of the Honolulu-Asia Aging Study[J].Ann Neurol,2002,52(2):168-174.
3. Iwamoto N,Nishiyama E,Ohwada J,et al.Demonstration of CRP immunoreactivity in brains of Alzheimer's disease:immunohistochemical study using formic acid pretreatment of tissue sections[J].Neurosci Lett,1994,177(1/2):23-26.
4. Inestrosa NC,Godoy JA,Quintanilla RA,et al.Peroxisome proliferator-activated receptor gamma is expressed in hippocampal neurons and its activation prevents beta-amyloid neurodegeneration:role of Wnt signaling[J].Exp Cell Res,2005,304(1):91-104.
5. 张玉霖,欧阳昌汉,吴基良,等.罗格列酮对散发性老年痴呆模型大鼠认知功能的影响[J].咸宁学院学报·医学版,2008,22(2):96-99.
6. Huang XR,Chung AC,Zhou L,et al.Latent TGF-beta1 protects against crescentic glomerulonephritis[J].J Am Soc Nephrol,2008,19(2):233-242.
7. Morley JE.Diabetes and aging:epidemiologic overview[J].Clin Geriatr Med,2008,24(3):395-405,v.
8. 王晓屏,高阳.老年性糖尿病辨治探析[J].辽宁中医杂志,2007,34(5):583-584.
9. Cukierman T,Gerstein HC,Williamson JD.Cognitive decline and dementia in diabetes——systematic overview of prospective observational studies[J].Diabetologia,2005,48(12):2460-2469.
10. Nakano S,Kuboki K,Matsumoto T,et al.Small,dense LDL and high-sensitivity C-reactive protein (hs-CRP) in metabolic syndrome with type 2 diabetes mellitus[J].J Atheroscler Thromb,2010,17(4):410-415.
11. Vepsäläinen T,Soinio M,Marniemi J,et al.Physical activity,high-sensitivity C-reactive protein,and total and cardiovascular disease mortality in type 2 diabetes[J].Diabetes Care,2011,34(7):1492-1496.
12. Komulainen P,Lakka TA,Kivipelto M,et al.Serum high sensitivity C-reactive protein and cognitive function in elderly women[J].Age Ageing,2007,36(4):443-448.
13. Lin HB,Yang XM,Li TJ,et al.Memory deficits and neurochemical changes induced by C-reactive protein in rats:implication in Alzheimer's disease[J].Psychopharmacology (Berl),2009,204(4):705-714.
14. Bi BT,Lin HB,Cheng YF,et al.Promotion of β-amyloid production by C-reactive protein and its implications in the early pathogenesis of Alzheimer's disease[J].Neurochem Int,2012,60(3):257-266.
15. Liu F,Chen HY,Huang XR,et al.C-reactive protein promotes diabetic kidney disease in a mouse model of type 1 diabetes[J].Diabetologia,2011,54(10):2713-2723.
16. 刘尊敬,杨期东,刘运海,等.过氧化小体增殖剂激活型受体 γ激活剂对缺血再灌注脑组织的保护作用及炎性机制分析[J].国际神经病学神经外科学杂志,2007,34(2):121-124.
17. Pathan AR,Gaikwad AB,Viswanad B,et al.Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats[J].Eur J Pharmacol,2008,589(1/2/3):176-179.
18. Pedersen WA,Mcmillan PJ,Kulstad JJ,et al.Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice[J].Exp Neurol,2006,199(2):265-273.
19. 张亭亭,刘丽萍,姜荔莹,等.罗格列酮改善链脲霉素诱导的糖尿病小鼠认知障碍及机制研究[J].神经药理学报,2011,1(2):1-6.
20. 谢英才,周和超,黄贵心.罗格列酮对胰岛素抵抗大鼠血清 C反应蛋白表达水平的抑制作用[J].中国现代医学杂志,2008,18(18):2622-2624.
21. 姚辉,林汉华,于芳,等.2型糖尿病大鼠血清 C反应蛋白动态变化及罗格列酮干预后改变[J].临床儿科杂志,2005,23(8):516-518.
22. Abdin AA,Baalash AA,Hamooda HE.Effects of rosiglitazone and aspirin on experimental model of induced type 2 diabetes in rats:focus on insulin resistance and inflammatory markers[J].J Diabetes Complications,2010,24(3):168-178.

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Research on the Mechanism of Rosiglitazone in Improving Cognitive Impairment in Senile Diabetic Rats

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