Objective To investigate the effect of diet-induced obesity on ischemia brain injury in mice.Methods A total of 60 male C57/Bl6 mice were treated with high-fat (high-fat group, n=30) or normal diet (control group, n=30) for three months, and each group was further divided into sham group and model group, with 15 mice in each subgroup. The model group was established the middle cerebral artery occlusion model. The nerve injury was evaluated with Neurologic Severity Score (NSS), the infarct volume was evaluated by 2,3,5- chlorinated three phenyl tetrazolium chloride (TTC) staining, the expression of sirtuin (Sirt1), Wnt and apoptosis inducing factor (AIF) were detected with Western blotting seven days after modeling.Results Seven days after modeling, the NSS was higher in the high-fat group than in the control group (t=10.053, P<; 0.05), and no significant difference was found in the infarct volume between two groups (t=6.872, P>; 0.05). The expression of Sirt1 (t=8.462, P<; 0.05) and AIF (t=8.471, P<; 0.05) was higher, and the expression of Wnt (t=17.752, P<; 0.01) was lower in the high-fat group than in the control group.Conclusion Obesity could affect the recovery of mice with MCAO, which may related with impaired Wnt signaling.
[1] Li W, Prakash R, Chawla D, et al.Early effects of high-fat diet on neurovascular function and focal ischemic brain injury[J]. Am J Physiol Regul Integr Comp Physiol, 2013, 304(11): R1001-R1008.
[2] 李琦,钟纯正. 急性缺血性脑卒中复发危险因素分析及低密度脂蛋白与高密度脂蛋白比值对脑卒中复发的预测价值[J]. 中国循环杂志, 2014, 29(9): 694-697.
[3] George MG, Tong X, Kuklina EV, et al.Trends in stroke hospitalizations and associated risk factors among children and young adults, 1995-2008[J]. Ann Neurol, 2011, 70(5): 713-721.
[4] Rani MU, Basha DC, Jamuna D.High fat diet influences spatial learning and brain cholinergic and antioxidant systems in male rats[J]. Trends Biotechnol, 2014, 8(8): 18-28.
[5] Chatzikonstantinou A, Ebert AD, Wolf ME.The impact of body mass index on the thrombolytic treatment of acute ischemic stroke[J]. Cerebrovasc Dis, 2016, 42(3-4): 240.
[6] Li W, Prakash R, Kellycobbs AI, et al.Adaptive cerebral neovascularization in a model of type 2 diabetes: relevance to focal cerebral ischemia[J]. Diabetes, 2010, 59(1): 228-235.
[7] Yeung ST, Myczek K, Kang AP, et al.Impact of hippocampal neuronal ablation on neurogenesis and cognition in the aged brain[J]. Neuroscience, 2014, 259(4): 214-222.
[8] Varela-Nallar L, Inestrosa NC.Wnt signaling in the regulation of adult hippocampal neurogenesis[J]. Front Cell Neurosci, 2013, 7(100): 100.
[9] 谈艳,薛雨平,陈文鹤,等. 运动、膳食干预对肥胖大鼠胰岛素抵抗作用机制的研究[J]. 中国运动医学杂志, 2014, 33(8): 797-803.
[10] 展佳愔,宋祥福,李金华. 单纯性肥胖大鼠动物模型的构建及血脂变化[J]. 中国实验诊断学, 2013, 17(4): 657-658.
[11] Peng Z, Li J, Li Y, et al.Downregulation of miR-181b in mouse brain following ischemic stroke induces neuroprotection against ischemic injury through targeting heat shock protein A5 and ubiquitin carboxyl-terminal hydrolase isozyme L1[J]. J Neurosci Res, 2013, 91(10): 1349.
[12] 彭志锋,王喜英,杨靖辉. 小鼠脑缺血时自噬相关基因5的抗损伤作用[J]. 中国病理生理杂志, 2016, 32(1): 64-68.
[13] Bing CY, Park JH, Ji HA, et al.Effects of high-fat diet on neuronal damage, gliosis, inflammatory process and oxidative stress in the hippocampus induced by transient cerebral ischemia[J]. Neurochem Res, 2014, 39(12): 2465-2478.
[14] Langdon KD, Clarke J, Corbett D.Long-term exposure to high fat diet is bad for your brain: exacerbation of focal ischemic brain injury[J]. Neuroscience, 2011, 182(182): 82-87.
[15] Snarska KK, Bachórzewskagajewska H, Kapicatopczewska K, et al.Hyperglycemia and diabetes have different impacts on outcome of ischemic and hemorrhagic stroke[J]. Arch Med Sci, 2017, 13(1): 100-108.
[16] Zuurbier SM, Hiltunen S, Tatlisumak T, et al.Admission hyperglycemia and clinical outcome in cerebral venous thrombosis[J]. Stroke, 2015, 47(6): e171.
[17] 杜军辉,马楼艳,李蓉. 自噬与血管生成的研究进展[J]. 转化医学杂志, 2017, 6(6): 381-384.
[18] Albahrani R, Tuertcher D, Zailaie S, et al.Differential SIRT1 expression in hepatocellular carcinomas and cholangiocarcinoma of the liver[J]. Ann Clin Lab Sci, 2015, 45(1): 3-9.
[19] Martins IJ, Wilson AC, Wei LFL, et al.Sirtuin-1 mediates the obesity induced risk of common degenerative diseases: Alzheimer's disease, coronary artery disease and type 2 diabetes[J]. Health, 2012, 4(12A): 1448-1456.
[20] Wauters E, SanchezArévalo Lobo VJ, Pinho AV, et al. Sirtuin-1 regulates acinar-to-ductal metaplasia and supports cancer cell viability in pancreatic cancer[J]. Cancer Res, 2013, 73(7): 2357.
[21] Muneer A.Wnt and GSK3 signaling pathways in bipolar disorder: Clinical and therapeutic implications[J]. Clin Psychopharmacol Neurosci, 2017, 15(2): 100.
[22] Gomez-Cambronero J, Kantonen S.A river runs through it: how autophagy, senescence, and phagocytosis could be linked to phospholipase D by Wnt signaling[J]. J Leukoc Biol, 2014, 96(5): 779-784.
[23] Ip W, Shao W, Chiang YT, et al.The Wnt signaling pathway effector TCF7L2 is upregulated by insulin and represses hepatic gluconeogenesis[J]. Am J Physiol Endocrinol Metab, 2012, 303(9): E1166.
[24] Chong ZZ, Hou J, Shang YC, et al.EPO relies upon novel signaling of Wnt1 that requires Akt1, FoxO3a, GSK-3ß, and ß-Catenin to foster vascular integrity during experimental diabetes[J]. Curr Neurovasc Res, 2011, 8(2): 103.
[25] Yu W, Bonnet M, Farso M, et al.The expression of apoptosis inducing factor (AIF) is associated with aging-related cell death in the cortex but not in the hippocampus in the TgCRND8 mouse model of Alzheimer's disease[J]. BMC Neurosci, 2014, 15(1): 73.
[26] Hu G, Wu Z, Yang F, et al.Ginsenoside Rd blocks AIF mitochondrio-nuclear translocation and NF-;#x003ba;B nuclear accumulation by inhibiting poly (ADP-ribose) polymerase-1 after focal cerebral ischemia in rats[J]. Neurol Sci, 2013, 34(12): 2101-2106.
