慢性寒冷暴露与小鼠心肌及脑血管的改变

摘要/Abstract

摘要： [摘要] 目的探讨慢性寒冷暴露对小鼠心脏及脑血管的影响，及寒冷诱导心脑血管疾病的相关机制。方法选择生后90～180d的成年雄性小鼠60只，随机分为正常对照组和寒冷暴露组两组，每组30只。寒冷暴露组置于温度为-1―4℃环境中饲养30d，建立慢性寒冷暴露模型。测量心脏指数(heart mass index, HMI)；采用血细胞分析仪检测血常规参数；化学发光法检测血清雌激素水平；HE染色法观察心肌细胞形态；墨汁灌注法观察脑血管体密度。结果慢性寒冷暴露可诱导小鼠心肌肥厚，脑血管体密度减少，白细胞、淋巴细胞、红细胞和血小板数目明显增多，对心脏和脑血管造成损伤。结论慢性寒冷暴露可导致心脏和脑血管的结构和功能改变，这与雌激素直接参与寒冷应激反应过程密切相关。

关键词: [关键词] 寒冷应激, 心脏指数, 脑血管体密度, 雌激素, 小鼠

Abstract: [Abstract] Objective: The study was tried to investigate the alterations of heart and cerebral vessels after chronic cold exposure in mice. In the meantime, the pathological mechanisms were discussed as well. Methods: Male mice of ages from 90 to 180 d were used, and 60 mice were divided into control group and cold exposure group in random. Cold exposure group was fed at temperature from -1℃ and 4 ℃ for 30 days to make the chronic cold exposure model. Then, heart mass index was measured. Blood routine analyses were detected using blood cell analyzer, and the serum estrogen levels were detected by chemiluminescence method. The histological structure of cardiomyocytes was visualized with hematoxylin-eosin（H. E.）staining, and the cerebral vasculature was visualized with ink perfusion assay. Results: Chronic cold exposure could induce mouse’s myocardial hypertrophy and decrease the cerebral vascular density. The number of white blood cells, lymphocytes, red blood cells and blood platelet increased, and estrogen level of blood increased as well, which contributed to the pathological alterations of cardiovascular system. Conclusion: Chronic cold exposure could induce myocardial hypertrophy and the alterations of blood cells, cerebral vasculature and estrogen. The pathological alterations of blood cells, cerebral vasculature and estrogen are involved in the production of myocardial hypertrophy.

Key words: [Key words] Chronic cold exposure, myocardial hypertrophy, Cerebral vasculature, Estrogen, Mouse

屈婷婷李瑞玲王颖周莉邓锦波邓洁心. 慢性寒冷暴露与小鼠心肌及脑血管的改变[J]. , 2016, 47(1): 80-86.

参考文献

[1] Planas AM, Soriano MA, Ferrer I, et al. Regionalex pression of inducible heat shock protein-70 mRNA in the rat brain following administration of convulsantdrugs [J]. Mol Brain Res, 1994, 27 (1): 127-137.

[2] Harinath K, Malhotra AS, Pal K, et a1. Autonomic Nervous System and Adrenal Response to cold in Man at Antarctica [J]. Wilderness Environ Med, 2005, 16(2):81-91.

[3] Richard E. Lee, Jr. Insect cold hardiness: to freeze or not to freeze [J]. Bioscience, 1989, 39(5): 308-313.

[4] 孙翊道,裴晓红,林珍.低温对人类健康的影响[J].医学研究通讯,1998,27(8):26?28.

[5] Wu JY, Ji AL, LYM, et a1. Effects of acute cold exposure on permeability of blood brain barrier and protection of luteolin in rats [J]. Medical Journal of National Defending Forces in Northwest China, 2008, 29(5): 364-367. (in Chinese)
吴佳颖,季爱玲,李运明,等.急性冷暴露对大鼠血脑屏障通透性的影响及木樨草素的保护作用[J].西北国防医学杂志,2008,29(5):364-367.

[6] Gao zh, Abulimiti Adilijiang, Uper Hamulati. Effect of dry and cold environment on the biological characterization of mice [J]. science＆Technology Review, 2008, 26(14): 84-87. (in Chinese)
高振,阿地力江-阿布力米提,哈木拉提-吾甫尔.干燥寒冷环境对小鼠生物表征的影响[J].科技导报,2008,26(14):84-87.

[7] Makinen TM, Palinkas LA, Reeves DL, et al Effect of repeated exposures to cold on cognitive performance in humans [ J]. PhysiolBehav, 2006 , 87( 1): 166- 176 .

[8] Danet SR, ichard F, Montaye M, et al. Unhealthy effects of atmospheric temperature and pressure on the occurrence of myocardial infarction and coronary deaths. A 10-year survey: the Lille-World Health Organization MONICA project (monitoring trends and determinants in cardiovascular disease) [J]. Circulation, 1999, 100 (l); El-7.

[9] Morabito M, Modesti PA, Cecchi L, et al. Relationships between weather and myocardial infarction: a biometeorological approach [J]. Int J Cardiol, 2005, 105 (3):288-293.

[10] Lee JH, Chae SC, Yang DH, et al. Influence of weather on daily hospital admissions for acute myocardial infarction (from the Korea Acute Myocardial Infarction Registry). Int J Cardiol, 2010,144(1):16-21.

[11] Charach G, Rabinovich PD, Weintraub M, Seasonal changes in blood pressure and frequency of related complications in elderly Israeli patients with essential hypertension [J]. Gerontology, 2004, 50 (5): 315-321.

[12] 王卉，王继厂，施睿臻，钟晓华，李庆平. 依那普利和厄贝沙坦对去势后大鼠心肌肥厚一氧化氮和一氧化氮合酶的影响[J].医学研究生学报，2010，23（7）：684-687.

[13] 张书余,王宝鉴,谢静芳,等.吉林省心脑血管疾病与气象条件关系分析和预报研究[J].气象, 2010,36(9): 106?110.

[14] 杨贤为,叶殿秀.我国心脑血管病的医学气象学研究[J].气象科技,2003,31(6):376?380.

[15] 谈建国,瞿惠春.猝死与气象条件的关系[J].气象科技,2003,31(1):58?61.

[16] NAIR N, BEDW AL S, PRASAD S, et al . Short term zinc deficiency in diet induces increased oxidative stress in testes and epididym is of rats [J]. Indian J Exp Biol , 2005, 43(9): 786－794.

[17] Saito S , Matsumiya G, Sakaguchi T, et al. Cardiac fibrosis and cellular hypertrophy decrease the degree of reverse remodeling and improvement in cardiac function during left ventricular assist. [J] Heart Lung Transplant, 2010, 29(6)∶ 672 -679

[18] Gjedde A, Diemer NH. Double-tracer study of the fine regional blood-brain glucose transfer in the rat by computer-assisted autoradiography [J]. J Cereb Blood Flow Metab , 1985,5:282-289.

[19] Brann D. W., Dhandapani K., Wakade C., Mahesh V. B., Khan M. M. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids. 2007. 72(5). 381-405

[20] Bums K. A., Korach K. S. Estrogen receptors and human disease: an update. Arch Toxicol. 2012. 86(10). 1491-1504

[21] Appelros P., Stegmayr B., Terent A. Sex differences in stroke epidemiology: a systematic review. Stroke. 2009. 40(4). 1082-1090

[22] Turtzo L. C., McCullough L. D. Sex differences in stroke. Cerebrovasc Dis. 2008. 26(5).462-474.

[23] Deng TX, Wang ZhX, Deng JB et al. The study of Sexual Difference Against Coldness [J]. Journal Medical Research, 2011,40(4):45-46. (in Chinese)
邓同兴,王志新,邓锦波等.耐寒性的性别差异性研究[J].医学研究杂志,2011,40(4):45-46.

[24] Vamvakopoulos NC, Chrousos GP. Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction. J Clin Invest. 1993. 92(4):1896-902.

[25] Bao AM, Fischer DF, Wu YH, Hol EM, Balesar R, Unmehopa UA, Zhou JN, Swaab DF. A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry. 2006. 11(6):567-76.

[26] Lu NZ, Eshleman AJ, Janowsky A, Bethea CL. Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques. Mol Psychiatry. 2003. 8(3):353-60.

[27] Pecins-Thompson M, Bethea CL. Ovarian steroid regulation of serotonin-1A autoreceptor messenger RNA expression in the dorsal raphe of rhesus macaques. Neuroscience. 1999. 89(1):267-77.

[28] Halbreich U, Tworek H. Altered serotonergic activity in women with dysphoric premenstrual syndromes. Int J Psychiatry Med. 1993.23(1):1-27.

[29] Lund TD, Munson DJ, Haldy ME, Handa RJ. Androgen inhibits, while oestrogen enhances, restraint-induced activation of neuropeptide neurones in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol. 2004. 16(3):272-8.

[30] Roy BN, Reid RL,Van Vugt DA. The effects of estrogen and progesterone on corticotropin-releasing hormone and arginine vasopressin messenger ribonucleic acid levels in the paraventricular nucleus and supraoptic nucleus of the rhesus monkey. Endocrinology. 1999.140(5):2191-8.

[31] Li XF, Mitchell JC, Wood S, Coen CW, Lightman SL, O’Byrne KT. The effect of oestradiol and progesterone on hypoglycaemic stress-induced suppression of pulsatile luteinizing hormone release and on corticotropin-releasing hormone mRNA expression in the rat. J Neuroendocrinol. 2003.15(5):468-76.

[32] Wang Q, Santizo R, Baughman VL, et al. Estrogen provides neuroprotection in transient forebrain ischemia through perfusion- independent mechanisms in rats [J]. Stroke, 1999, 30: 630-637.

[33] Alkayed NJ, Harukuni I, Kimes AS, et al. Gender-linked brain injury in experimental stroke [J]. Stroke, 1998, 29:159-165.

[34] Rusa R, Alkayed NJ, Grain BJ, et, al. 17β-estradiol reduces stroke injury in estrogen-deficient female animals [J]. Stroke, 1999, 30:1665-1670.

[35] McNeill AM, Kim N, Duckies SP, et al. Chronic estrogen treatment increases levels of endothelial nitric oxide synthase protein in rat cerebral microvessels [J]. Stroke, 1999, 30:2186-2190.

[36] Arias-Loza P. A., Muehlfelder M., Pelzer T. Estrogen and estrogen receptors in cardiovascular oxidative stress. Pflugers Arch. 2013.