罗格列酮干预胰岛素抵抗大鼠认知行为及AD样病变的作用机制

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Abstract Objective To study the insulin resistance rat cognitive behavior and hippocampal Alzheimer disease (AD) - like pathological change, to study the intervention effect of rosiglitazone (RSG) on the cognitive and AD- like lesions and its possible mechanism. Methods The rat models of insulin resistance were established and 20 successful models were randomly divided into the insulin resistance(IR)group(n=10) and rosiglitazone (RSG) group, each group of 10,the normal rats as control (CTL)group(n=10).The rats in RSG group were given high-protein diet with high fat and sugar +RSG 3 mg/kg/d by gavage for 4 weeks. IR group were given high-protein diet with high fat and sugar + equivalent saline by gavage for 4 weeks.CTL group were given general diet + equivalent saline by gavage for 4 weeks. The observation indexes included the blood glucose,plasma insulin levels(FINS),insulin resistance index(IRI),Morris water maze test,insulin degrading enzyme (IDE),response to insulin sialing pathway of pAKT,and Aβ protein expression in hippocampus. Results The IRI in IR group and RSG group(8.56±0.43 and 3.82±0.38)is low than that in CTL group(2.27±0.25),but in RSG group was lower than in IR group. The 4 day escape latency of rats in IR and RSG groups[(63.21±5.67)s and(37.48±5.41)s] was significantly longer than in CTL group [(24.14±5.49)s].The through the platform quadrant percentage of total time in IR and RSG groups [(21.88±3.85)% and (33.43±2.98)%] was smaller than in CTL group [(39.57±4.31)%],but RSG group is superior to IR group. The Aβ protein expressions in IR group and RSG groups (0.27±0.023 and 0.56±0.011)was stronger than that in CTL group(0.13±0.021), but RSG group is weaker than IR group. These differences were statistically significant (P<0.01 or P<0.05). Conclusions Insulin resistance rats can develop cognitive behavior decrease and aβ deposition AD like pathological changes.RSG can improve the cognitive behavior, reduce the aβ in the hippocampus of deposition, its mechanism may be through the insulin pathway mediated by IDE PI3K/AKT,to enhance IDE of aβ, thereby reducing degradation deposition.

Key words： rosiglitazone insulin resistance Alzheimer′s disease insulin degrading enzyme

Received: 28 November 2015

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	Articles by authors
	YIN Liying
	LIU Zhixian
	NING Qingmei
	and CHEN li

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YIN Liying,LIU Zhixian,NING Qingmei等. Mechanisms of rosiglitazone intervening in insulin resistance in cognitive-behavioral and AD-like lesion in rats[J]. Med. J. Chin. Peop. Armed Poli. Forc., 2016, 27(5): 465-468.

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http://journal08.magtechjournal.com/Jwk_wjyx/EN/ OR http://journal08.magtechjournal.com/Jwk_wjyx/EN/Y2016/V27/I5/465

[1]	李钦云,陈征,张守字, 等. 126例阿尔茨海默病患者血脂代谢和胰岛素抵抗的研究[J]. 中华全科医学,2015,13(1):15-17.
[2]	杨雁,张晓洁,王玉萍,等. 噻唑烷二酮通过Wnt通路改善2型糖尿病大鼠海马阿尔茨海默病样病变[J]. 中国病理生理杂志,2010,26(12):2421-2427.
[3]	冉军,王萍. 脑脊液tau蛋白联合Aβ1～42在阿尔茨海默病诊断中的价值[J]. 中国老年学杂志,2015,35(10):2697-2698.
[4]	Fernández-Gamba A,Leal M C,Morelli L,et al. Insulin-degrading enzyme: structure-function relationship and its possible roles in health and disease [J]. Curr Pharm Des,2009,15(31):3644-3655.
[5]	Zhao L,Teter B,Morihara T,et al. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer’s disease intervention [J]. J Neurosci,2004,24(49):11 120-11 126.
[6]	王俊亚,张冬梅. Morris水迷宫实验的测试方法介绍及注意事项[J]. 现代医药卫生,2012,28(21):3289-3290.
[7]	杨文清,马晶,宋晓征,等. 罗格列酮调节IDE和GSK-3β的活性改善阿尔茨海默病动物认知能力[J]. 重庆医科大学学报,2013,38(6):620-625.
[8]	Darshini M,Kamal M A,Greig N H, et al. Alzheimer′s disease and type 2 diabetes: exploring the association to obesity and tyrosine hydroxylase [J]. CNS Neurol Disord Drug Targets,2012,11(4):482-489.
[9]	杨思思,姜腾,张木勋. 肥胖大鼠海马内TNF-α、胰岛素降解酶、PPARγ和Aβ的表达及其作用[J]. 中国病理生理杂志,2012,28(10):1756-1760.