Luteolin Cải Thiện Rối Loạn Nhận Thức Bằng Cách Ức Chế Sự Biểu Hiện Của Các Cytokine Viêm Và Tăng Cường Nồng Độ Proteins Liên Quan Đến Synapse GAP-43 Và SYN Trong Mô Hình Chuột Bị Đái Tháo Đường Do Streptozotocin Gây Ra

Neurochemical Research - Tập 43 - Trang 1905-1913 - 2018
Jing-xue Gu1,2, Xiao-jing Cheng1,2, Xuan Luo1,2, Xia Yang1,2, Yi-peng Pang1,2, Xiao-fei Zhang1,2, Yu-yun Zhang1,2, Yi Liu1,2
1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China
2Department of Pathology, Xuzhou Medical University, Xuzhou, China

Tóm tắt

Luteolin, một flavonoid được chiết xuất từ Cirsium japonicum, có hoạt tính chống oxy hóa, chống viêm và bảo vệ thần kinh. Các nghiên cứu trước đây của chúng tôi đã cho thấy luteolin có lợi cho chuột bị đái tháo đường với các rối loạn nhận thức. Trong nghiên cứu này, chúng tôi đã khảo sát xem luteolin có thể ức chế các cytokine viêm, từ đó tăng cường các protein liên quan đến synapse trong mô hình chuột bị đái tháo đường do streptozotocin (STZ) gây ra hay không. Các con chuột trong mô hình được điều trị bằng luteolin trong 8 tuần liên tiếp, sau đó đánh giá khả năng nhận thức qua bài kiểm tra MWM. Nhuộm Nissl được sử dụng để đánh giá những thay đổi về mặt thần kinh bệnh lý trong hồi hải mã và các tác động của luteolin lên chuột bị đái tháo đường. Khi các động vật bị hiến tế, sự biểu hiện của các cytokine viêm bao gồm interleukin-1β (IL-1β) và yếu tố hoại tử khối u-α (TNF-α) và các protein liên quan đến synapse bao gồm protein liên quan đến tăng trưởng-43 (GAP-43) và synaptophysin (SYN) được xác định. Kết quả cho thấy sự cải thiện của các hoạt động hành vi trong bài kiểm tra MWM, giảm biểu hiện của các sản phẩm cuối glycation (AGEs) trong huyết tương và thụ thể cho các sản phẩm cuối glycation tiên tiến trong hồi hải mã, ức chế IL-1β và TNF-α ở cả hồi hải mã và huyết tương trong chuột bị đái tháo đường. Hơn nữa, điều trị bằng luteolin đã tăng cường sự biểu hiện của GAP-43 và SYN trong hồi hải mã. Do đó, luteolin có thể cải thiện rối loạn chức năng nhận thức trong mô hình chuột bị đái tháo đường do STZ gây ra.

Từ khóa

#luteolin #đái tháo đường #cytokine viêm #protein liên quan đến synapse #chuột mô hình

Tài liệu tham khảo

Koekkoek PS, Kappelle LJ, Berg EVD, Rutten GEHM, Biessels GJ (2015) Cognitive function in patients with diabetes mellitus: guidance for daily care. Lancet Neurol 14(3):329–340 Ryo S, Ferris HA, Chee MJ, Eleftheria MF, C Ronald K (2013) Reduction of the cholesterol sensor SCAP in the brains of mice causes impaired synaptic transmission and altered cognitive function. PLoS Biol 11(4):e1001532 Qiu C, Sigurdsson S, Zhang Q, Jonsdottir MK, Kjartansson O, Eiriksdottir G, Garcia ME, Harris TB, Buchem MA, Gudnason V (2014) Diabetes, markers of brain pathology and cognitive function. Ann Neurol 75(1):138–146 Jacobson AM, Ryan CM, Cleary PA, Waberski BH, Weinger K, Musen G, Dahms W, Group AE (2011) Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. Diabetologia 54(2):245–255 Cukierman T, Gerstein HC, Williamson JD (2005) Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies. Diabetologia 48(12):2460–2469 Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B, Sulkava R, Kivipelto M(2010) Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 75(13):1195–1202 Kalalian-Moghaddam H, Baluchnejadmojarad T, Roghani M, Goshadrou F, Ronaghi A (2012) Hippocampal synaptic plasticity restoration and anti-apoptotic effect underlie berberine improvement of learning and memory in streptozotocin-diabetic rats. Eur J Pharmacol 698(1–3):259–266 Zhao CH, Liu HQ, Cao R, Ji AL, Zhang L, Wang F, Yang RH (2012) Effects of dietary fish oil on learning function and apoptosis of hippocampal pyramidal neurons in streptozotocin-diabetic rats. Brain Res 1457(2):33–43 Critchley JA, Restrepo BI, Ronacher K, Kapur A, Bremer AA, Schlesinger LS, Basaraba R, Kornfeld H, van Crevel R (2017) Defining a research agenda to address the converging epidemics of tuberculosis and diabetes. Part 2: underlying biological mechanisms. Chest 152:165–173 Stirban A, Gawlowski T, Roden M (2014) Vascular effects of advanced glycation endproducts: clinical effects and molecular mechanisms. Mol Metab 3(2):94–108 Li XH, Lv BL, Xie JZ, Jing L, Zhou XW, Wang JZ (2012) AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation. Neurobiol Aging 33(7):1400–1410 Vieira VJ, Valentine RJ, Wilund KR, Antao N, Baynard T, Woods JA (2009) Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice. Am J Physiol Endocrinol Metab 296(5):E1164–E1171 Pancani T, Anderson KL, Brewer LD, Kadish I, Demoll C, Landfield PW, Blalock EM, Porter NM, Thibault O (2013) Effect of high-fat diet on metabolic indices, cognition, and neuronal physiology in aging F344 rats. Neurobiol Aging 34(8):1977–1987 Sama MA, Mathis DM, Furman JL, Hafiz Mohmmad A, Artiushin IA, Kraner SD, Norris CM (2008) Interleukin-1beta-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity. J Biol Chem 283(32):21953–21964 Hennessy E, Griffin ÉW, Cunningham C (2015) Astrocytes are primed by chronic neurodegeneration to produce exaggerated chemokine and cell infiltration responses to acute stimulation with the cytokines IL-1 and TNF. J Neurosci 35(22):8411–8422 Alexander K, Clarissa VH, Marco S, Annalena T, Nadine P, Mariya K, Aarne F, Spies CD (2013) Acetylcholinesterase inhibitors reduce neuroinflammation and -degeneration in the cortex and hippocampus of a surgery stress rat model. PLoS ONE 8(5):e62679–e62679 Barnum CJ, Tansey MG (2011) The duality of TNF signaling outcomes in the brain: potential mechanisms? Exp Neurol 229(2):198–200 Mrak RE, Griffin WS (2005) Glia and their cytokines in progression of neurodegeneration. Neurobiol Aging 26(3):349–354 Pickering M, Cumiskey D, O’Connor JJ (2005) Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol 90(5):663–670 Lynch MA (1999) What is the biological significance of an age-related increase in IL-1beta in hippocampus? Mol Psychiatry 4(1):15–18 Grasselli G (2013) Structural plasticity of climbing fibers and the growth-associated protein GAP-43. Front Neural Circuits 7(6):25 Zhou J, Wang L, Ling S, Zhang X (2007) Expression changes of growth-associated protein-43 (GAP-43) and mitogen-activated protein kinase phosphatase-1 (MKP-1) and in hippocampus of streptozotocin-induced diabetic cognitive impairment rats. Exp Neurol 206(2):201–208 Basu J, Siegelbaum SA (2015) The corticohippocampal circuit, synaptic plasticity, and memory. Cold Spring Harb Perspect Biol 7(11):a021733 Hou Y, Zhou L, Yang QD, Du XP, Li M, Yuan M, Zhou ZW (2012) Changes in hippocampal synapses and learning-memory abilities in a streptozotocin-treated rat model and intervention by using fasudil hydrochloride. Neuroscience 200(1):120–129 Li C, Liu S, Guan Y, Qian W, Du F, Hou X (2009) Long pulse gastric electrical stimulation induces regeneration of myenteric plexus synaptic vesicles in diabetic rats. Neurogastroenterol Motil 22(4):453–461 Saebyeol J, Kelley KW, Johnson RW (2008) Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci USA 105(21):7534–7539 Dirscherl K, Karlstetter M, Ebert S, Kraus D, Hlawatsch J, Walczak Y, Moehle C, Fuchshofer R, Langmann T (2012) Correction: Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype. J Neuroinflamm 9(1):72–79 Jang S, Dilger RN, Johnson RW (2010) Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice 1, 2, 3. J Nutr 140(10):1892–1898 Liu Y, Tian X, Gou L, Sun L, Xin L, Yin X (2013) Luteolin attenuates diabetes-associated cognitive decline in rats. Brain Res Bull 94(9):23–29 Zheng S, Han F, Shi Y, Wen L, Han D (2017) Single-prolonged-stress-induced changes in autophagy-related proteins beclin-1, LC3, and p62 in the medial prefrontal cortex of rats with post-traumatic stress disorder. J Mol Neurosci 62:1–12 Meng Z, Zhang Y, Wei Z, Liu P, Kang J, Zhang Y, Ma D, Ke C, Chen Y, Luo J (2017) High serum resistin associates with intrahepatic inflammation and necrosis: an index of disease severity for patients with chronic HBV infection. BMC Gastroenterol 17(1):6 Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625 Lin M, Chen Y, Jin J, Hu Y, Zhou KK, Zhu M, Le YZ, Ge J, Johnson RS, Ma JX (2011) Ischaemia-induced retinal neovascularisation and diabetic retinopathy in mice with conditional knockout of hypoxia-inducible factor-1 in retinal Muller cells. Diabetologia 54(6):1554–1566 Pickering RJ, Rosado CJ, Sharma A, Buksh S, Tate M, De JH (2018) Recent novel approaches to limit oxidative stress and inflammation in diabetic complications. Clin Transl Immunol 7(4):e1016 Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741 刘灿: 老年抑郁患者认知功能与IL-1β水平相关性研究. 中华医学研究杂志 (2012) Kulkarni MJ, Korwar AM, Mary S, Bhonsle HS, Giri AP (2013) Glycated proteome: from reaction to intervention. Proteom Clin Appl 7(1–2):155–170 Šebeková K, Stürmer M, Fazeli G, Bahner U, Stäb F, Heidland A (2015) Is vitamin D deficiency related to accumulation of advanced glycation end products, markers of inflammation, and oxidative stress in diabetic subjects? Biomed Res Int. https://doi.org/10.1155/2015/958097 Makita Z, Vlassara H, Cerami A, Bucala R (1992) Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem 267(8):5133–5138 Santilli F, Vazzana N, Bucciarelli LG, Davì G (2009) Soluble forms of RAGE in human diseases: clinical and therapeutical implications. Curr Med Chem 16(8):940–952 Muhammad S, Bierhaus A, Schwaninger M (2009) Reactive oxygen species in diabetes-induced vascular damage, stroke, and Alzheimer’s disease. J Alzheimers Dis 16(4):775–785 Manuela A, Raffaella M, Claudio M, Francesca R, Catalano MG, Nicoletta P, Oliviero D, Giuseppe B (2005) Up-regulation of advanced glycated products receptors in the brain of diabetic rats is prevented by antioxidant treatment. Endocrinology 146(12):5561–5567 Wang SH, Sun ZY (2009) Diabetes impairs hippocampal function via advanced glycation end product mediated new neuron generation in animals with diabetes-related depression. Toxicol Sci 111(1):72–79 Coggins PJ, Zwiers H (1991) B-50 (GAP-43): biochemistry and functional neurochemistry of a neuron-specific phosphoprotein. J Neurochem 56(4):1095–1106 Hung CC, Lin CH, Chang H, Wang CY, Lin SH, Hsu PC, Sun YY, Lin TN, Shie FS, Kao LS (2016) Astrocytic GAP43 induced by the TLR4/NF-κB/STAT3 axis attenuates astrogliosis-mediated microglial activation and neurotoxicity. J Neurosci 36(6):2027–2043 Claes-Goran O, Herbert G, Laura S, Annika T, Tamas B (2006) Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients. Diabetes 55(2):435–440