肌肽对糖尿病大鼠海马中氧化应激及NF-κB信号通路的影响

doi:10.13418/j.issn.1001-165x.2018.05.007

Abstract

Abstract:

Objective To investigate the effect of Carnosine (CAR) on cognitive function and oxidative stress and NF-κB signaling pathway in diabetic rats. Methods Fifty male SD rats, except the normal group (n=8), were given high fat and sugar diet, and intraperitioneal injection of STZ to establish type Ⅱ diabetes rats. The rats were randomly divided into the diabetic model group and Carnosine groups with different doses (100, 300 and 900 mg/kg). All drugs were administrated for 56 days. The behavior tests were performed on the Morris water maze method. HE stain were used to observe the pathological changes of the hippocampus. The activity of SOD and the content of MDA in the hippocampus were detected by respective commercial kits. The content of GSH and carnosine in hippocampus tissue were detected by HPLC. Western Blot were used to detect the expression of TNF-α, IL-1β in cytoplasm and NF-κB p65 in nucleus. Results Compared with diabetic group, Carnosine groups improved significantly learning and memory ability and the morphology of hippocampal neuronal cell in diabetic rats, enhanced the activity of SOD, the content of GSH and carnosine in the hippocampus of diabetic rats, inhibited the content of MDA, which, at the same time, reduced significantly the nuclear transfer of NF-κB with the nucleus of hippocampus in diabetic rats and down-regulated the expression of downstream inflammatory cytokines TNF-α and IL-1β. Conclusion Carnosine may prevent cognitive dysfunction in DM rats. The mechanism may be in connection with its function that it can inhibit oxidative stress, reduce NF-κB translocating into the nucleus and the expression of TNF-α and IL-1β.

Key words: Carnosine, 　Cognitive impairment; , NF-κB; , TNF-α, , IL-1β; , SOD; , MDA

ZHAO Dan-ting, LIU Ying, ZHAO Yan, LU Mei-li, YANG Wen-qiang, HE Xin，YANG Jing. Effect of Carnosine on oxidative stress and NF-κB signaling pathway in hippocampus of diabetic rats[J]. Chinese Journal Of Clinical Anatomy, 2018, 36(5): 514-519.

References

[1] Baranowski BJ, Hayward GC, Fajardo VA, et al. Increased prevalence of obesity/type 2 diabetes and lower levels of lithium in rural texas counties may explain greater alzheimer's disease risk[J]. J Alzheimers Dis, 2018, 64(1): 302-308.
[2] Asmat U, Abad K, Ismail K. Diabetes mellitus and oxidative stress-a concise review[J]. Saudi Pharm J, 2016, 24(5): 547-553.
[3] Caamaño J, Hunter CA. NF-kappaB family of transcription factors: cetral regulators of innate and adaptive immune functions[J]. Clin Microbiol Rev, 2002, 15(3): 414-429.
[4] Pekcein C, Kiray M, Ergur BU, et al. Carnosine attenuates oxidative stress and ap-optosis in transient cerebral ischemia in rats[J]. Acta Biol Hung, 2009, 60(2): 137-148.
[5] Xie RX, Li DW, Liu XC, et al. Carnosine attenuates brain oxidative stress and apoptosis after intracerebral hemorrhage in rats[J]. Neurochem Res, 2017, 42(2): 541-551.
[6] 李宗泽, 杨清俊, 朱艳凌, 等. 肌肽对高糖诱导SH-SY5Y细胞凋亡的保护作用[J].中国药理学与毒理学杂志, 2013, 27(5): 795-800.
[7] 方超, 李晴, 鲁美丽, 等. 肌肽对大鼠脑片缺氧缺糖/再灌损伤的保护作用[J]. 中国生化药物杂志, 2015, 35(9): 41-47.
[8] Lopachev AV, Lopacheva OM, Abaimov DA, et al. Neuroprotective effect of carnosine on primary culture of rat cerebellar cells under oxidative stress[J]. Biochemistry (Mosc), 2016, 81(5): 511-520.
[9] Skovsø S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin[J]. J Diabetes Investig, 2014, 5(4): 349-358.
[10]Tang Y, Yu C, Wu J, et al. Lychee seed extract protects against neuronal injury and improves cognitive function in rats with type II diabetes mellitus with cognitive impairment[J]. Int J Mol Med, 2018, 41(1): 251-263.
[11]杨菁, 吴国强, 白剑, 等. 邻苯二甲醛柱前衍生化高效液相色谱法测定组织中肌肽含量[J]. 中国生化药物杂志, 2009, 30(4): 258-260.
[12] Zhou Y, Luo Y, Dai J. Axonal and dendritic changes are asso-ciated with diabetic encephalopathy in rats: an important risl factor for Alzheimer’s disease[J]. J Alzhimers Dis, 2013, 34(4): 937-947.
[13] Ragy MM, Kamal NN. Linking senile dementia to type 2 diabetes: role of oxidative stress markers, C-reactive protein and tumor necrosis factor-α[J]. Neurol Res, 2017, 39(7): 587-595.
[14] Nicoletti VG, Santoro AM, Grasso G, et al. Carnosine interaction with nitric oxide and astroglial cell protection[J]. J Neurosci Res, 2007, 85(10): 2239-2245.
[15]王晓晨, 吉爱国. NF-κB信号通路与炎症反应[J]. 生理科学进展, 2014, 45(1): 68-71.
[16]Mattson MP, Camandola S. NF-κB in neuronal plasticity and neurodegenerative disorders[J]. J Clin Invest, 2001, 107(3): 247-254.
[17] Pozniak PD, White MK, Khalili K. TNF-α/NF-κB signaling in the CNS: possible connection to EPHB2[J]. J Neuroimmune Pharmacol, 2014, 9(2): 133-141.

Effect of Carnosine on oxidative stress and NF-κB signaling pathway in hippocampus of diabetic rats

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