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

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.	張玉霖,歐陽昌漢,吳基良,等.羅格列酮對散發性老年癡呆模型大鼠認知功能的影響[J].咸寧學院學報·醫學版,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.	王曉屏,高陽.老年性糖尿病辨治探析[J].遼寧中醫雜志,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.	Veps?l?inen 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.	劉尊敬,楊期東,劉運海,等.過氧化小體增殖劑激活型受體 γ激活劑對缺血再灌注腦組織的保護作用及炎性機制分析[J].國際神經病學神經外科學雜志,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.	張亭亭,劉麗萍,姜荔瑩,等.羅格列酮改善鏈脲霉素誘導的糖尿病小鼠認知障礙及機制研究[J].神經藥理學報,2011,1(2):1-6.
20.	謝英才,周和超,黃貴心.羅格列酮對胰島素抵抗大鼠血清 C反應蛋白表達水平的抑制作用[J].中國現代醫學雜志,2008,18(18):2622-2624.
21.	姚輝,林漢華,于芳,等.2型糖尿病大鼠血清 C反應蛋白動態變化及羅格列酮干預后改變[J].臨床兒科雜志,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.

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. 張玉霖,歐陽昌漢,吳基良,等.羅格列酮對散發性老年癡呆模型大鼠認知功能的影響[J].咸寧學院學報·醫學版,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. 王曉屏,高陽.老年性糖尿病辨治探析[J].遼寧中醫雜志,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. Veps?l?inen 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. 劉尊敬,楊期東,劉運海,等.過氧化小體增殖劑激活型受體 γ激活劑對缺血再灌注腦組織的保護作用及炎性機制分析[J].國際神經病學神經外科學雜志,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. 張亭亭,劉麗萍,姜荔瑩,等.羅格列酮改善鏈脲霉素誘導的糖尿病小鼠認知障礙及機制研究[J].神經藥理學報,2011,1(2):1-6.
20. 謝英才,周和超,黃貴心.羅格列酮對胰島素抵抗大鼠血清 C反應蛋白表達水平的抑制作用[J].中國現代醫學雜志,2008,18(18):2622-2624.
21. 姚輝,林漢華,于芳,等.2型糖尿病大鼠血清 C反應蛋白動態變化及羅格列酮干預后改變[J].臨床兒科雜志,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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