|本期目录/Table of Contents|

[1]张 宇,李 新,冷 晓,等.同型半胱氨酸对自发性高血压大鼠脑组织损伤免疫调节机制的研究[J].天津医科大学学报,2018,24(05):404-408.
 ZHANG Yu,LI Xin,LENG Xiao,et al.Study on the immunomodulatory mechanism of homocysteine in brain tissue injury in spontaneously hypertensive rats[J].Journal of Tianjin Medical University,2018,24(05):404-408.
点击复制

同型半胱氨酸对自发性高血压大鼠脑组织损伤免疫调节机制的研究(PDF)
分享到:

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
24
期数:
2018年05期
页码:
404-408
栏目:
基础医学
出版日期:
2018-09-20

文章信息/Info

Title:
Study on the immunomodulatory mechanism of homocysteine in brain tissue injury in spontaneously hypertensive rats
作者:
张 宇李 新冷 晓王 林
天津医科大学第二医院干部保健科, 天津市老年病学研究所, 天津 300211
Author(s):
ZHANG Yu LI Xin LENG Xiao WANG Lin
Department of Geriatrics, The Second Hospital, Tianjin Medical University, Tianjin 300211,China
关键词:
同型半胱氨酸自发性高血压大鼠免疫机制
Keywords:
homocysteine (Hcy)spontaneously hypertensive rats (SHR) immune mechanism
分类号:
R544.1
DOI:
-
文献标志码:
A
摘要:
目的:探讨同型半胱氨酸(Hcy)对自发性高血压(SHR)大鼠脑组织损伤的免疫调节机制。方法:取60只SHR大鼠,随机分为SHR-C(对照组)、SHR-M(高蛋氨酸组)和SHR-T(治疗组),每组20只。SHR-C普通饲料喂养,SHR-M给予2 mg/(kg·d)高蛋氨酸饮食。SHR-T组前8周给予2 mg/(kg·d)高蛋氨酸饮食,第9周开始给予叶酸4 mg/(kg·d)、维生素B12(VB12)0.09 mg/(kg·d)、维生素B6(VB6)0.09 mg/(kg·d)灌胃治疗。分别于第0、8、16周检测3组大鼠的体质量、收缩压(SBP)和血浆Hcy浓度。分别于第8、16周用ELISA测血浆中的IL-17和IL-10,实时定量PCR(Q-PCR)检测脑组织中IL-17和IL-10。第16周,免疫组织化学染色法检测脑组织中IL-17和IL-10表达情况。结果:第8周,SHR-M和SHR-T的体质量显著低于SHR-C,血浆Hcy浓度显著高于SHR-T,血浆IL-17浓度显著高于SHR-C,血浆IL-10浓度显著低于SHR-C,脑组织IL-10表达水平显著低于SHR-C(均P<0.05);SHR-M和SHR-T各参数差异没有统计学意义(P>0.05)。第16周,经治疗后SHR-T组的体质量升高、血浆Hcy浓度下降,与SHR-M组比较具有显著性差异(P<0.05);SHR-T组的血浆IL-17浓度降低、IL-10浓度升高,与SHR-M组比较具有显著性差异(P<0.05);SHR-T组脑组织IL-17表达水平显著低于SHR-M组,IL-10表达水平显著高于SHR-M组(P>0.05);SHR-M的脑组织IL-17细胞阳性率明显高于SHR-C和SHR-T,IL-10细胞阳性率明显高于SHR-C和SHR-T。结论:高同型半胱氨酸血症可促进炎症反应从而导致脑组织病变的发生,下调免疫反应后可起到保护作用。
Abstract:
Objective: To explore the immunomodulatory mechanism of homocysteine (Hcy) in brain tissue injury in spontaneously hypertensive rats SHR rats. Methods: Sixty SHR rats were randomly divided into SHR-C (control group), SHR-M (high methionine group) and SHR-T (treatment group), with 20 rats in each group. SHR-C was fed with ordinary diet and SHR-M was given to 2 mg/(kg·d) high methionine diet. SHR-T was given 2 mg/ (kg·d) high methionine diet for the first 8 weeks, and folic acid 4 mg/(kg·d) , vitamin B12 (VB12) 0.09 mg /(kg·d) and vitamin B6 (VB6) were intragastrically administered from week 9. The body weight, systolic blood pressure (SBP) and plasma Hcy concentration in three groups were measured at 0, 8th and 16th weeks, respectively. Enzyme-linked and immunosorbent assay (ELISA) was used to detect the plasma concentration levels of IL-17 and IL-10 at 8th and 16th weeks, and real-time quantitative PCR (Q-PCR) was applied to detected the mRNA levels in the brain tissues. The expression of IL-17 and IL-10 in brain tissue were detected by immunohistochemical staining at week 16. Results: At the 8th week, the body weight of SHR-M and SHR-T was significantly lower than that of SHR-C, and plasma Hcy concentration was significantly higher than that of SHR-T, and plasma IL-17 concentration higher than that of SHR-T, and plasma IL-17 concentration higher than that of SHR-T (all P <0.05). However, there was no significant difference between all parameters of SHR-M and SHR-T at the 8th week (P >0.05). At the 16th week, the body weight of SHR-T increased, and the Hcy concentration decreased after treatment, which were significantly different from those of SHR-M (P < 0.05); the plasma IL-17 concentration of SHR-T decreased and IL-10 concentration increased, which were statistically significant compared with SHR-M (P < 0.05); the mRNA expression level of IL-17 of SHR-T in brain tissue samples was significantly lower than that of SHR-M, and the expression level of IL-10 was significantly higher than that of SHR-M (P >0.05); the positive rate of IL-17 cells of SHR-M was higher than that of SHR-C and SHR-T in the brain tissue (P <0.05), and the positive rate of IL-10 cells was higher. Conclusion: Hcy can promote the inflammatory response and lead to the development of brain tissue, and it can play a protective role after reducing the immune response.

参考文献/References:


[1] Ganguly P, Alam S F, Role of homocysteine in the development of cardiovascular disease[J]. Nutr J, 2015,14: 6
[2] He L M, Gao C Y, Wang Y, et al. Red cell distribution width and homocysteine act as independent risk factors for cardiovascular events in newly diagnostic essential hypertension[J]. Oncotarget, 2017,8(60):102590
[3] Li S, Zhu J, Wu L, et al. The association between Plasma homocysteine and ambulatory blood Pressure variability in Patients with untreated hypertension[J]. Clin Chim Acta, 2017,477: 32
[4] Kirabo A. A new paradigm of sodium regulation in inflammation and hypertension[J]. Am J Physiol Regul Integr ComP Physiol, 2017, 313(6): R706
[5] Bartoloni E, Alunno A , Gerli R. Hypertension as a cardiovascular risk factor in autoimmune rheumatic diseases[J]. Nat Rev Cardiol, 2018,15(1): 33
[6] 张宇,王林. 同型半胱氨酸与H型高血压研究进展[J]. 中华老年病研究电子杂志, 2016, 3(1): 30
[7] Li Q, Wang Y, Yu F, et al. Peripheral Th17/Treg imbalance in patients with atherosclerotic cerebral infarction[J]. Int J Clin ExP Pathol, 2013,6(6): 1015
[8] Lehmann M, Regland B, Blennow K, et al. Vitamin B12-B6-folate treatment improves blood-brain barrier function in patients with hyperhomocysteinaemia and mild cognitive impairment[J]. Dement Geriatr Cogn Disord, 2003,16(3): 145
[9] Werder S F. Cobalamin deficiency, hyperhomocysteinemia, and dementia[J]. Neuropsychiatr Dis Treat, 2010,6: 159
[10] Miwa K, Tanaka M, Okazaki S, et al. Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors[J]. J Alzheimers Dis, 2016,49(2): 503
[11] Kayacelebi A A, Willers J, Pham V V, et al. Plasma homoarginine, arginine, asymmetric dimethylarginine and total homocysteine interrelationships in rheumatoid arthritis, coronary artery disease and Peripheral artery occlusion disease[J]. Amino Acids, 2015, 47(9): 1885
[12] Liu J, Liu H, Zhao H, et al. Relationship between cardio-ankle vascular index and homocysteine in hypertension subjects with hyperhomocysteinemia[J]. Clin Exp Hypertens, 2016,38(7): 652
[13] 徐志红,陆国平,吴春芳. 高同型半胱氨酸血症对内皮细胞炎症反应的促发作用及其干预性研究[J]. 上海医学, 2007, 15(5): 353
[14] 孔炜,王宪.免疫炎症反应与动脉粥样硬化—高同型半胱氨酸血症促进动脉粥样硬化早期发病的免疫炎症机制[J]. 中国动脉硬化杂志, 2007,15(7): 525
[15] Xie L, Choudhury G R, Winters A, et al. Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10[J]. Eur J Immunol , 2015,45(1): 180
[16] Ferlazzo V, D’Agostino P, Milano S, et al. Anti-inflammatory effects of annexin-1: stimulation of IL-10 release and inhibition of nitric oxide synthesis[J]. Int l Immunopharmacol , 2003, 3(10/11): 1363
[17] Beringer A, Noack M, Miossec P, et al. IL-17 in chronic inflammation: from discovery to targeting[J]. Trends Mol Med , 2016, 22(3): 230
[18] Wojkowska D W, Szpakowski P, Glabinski A, et al. Glabinski, interleukin 17A promotes lymphocytes adhesion and induces CCL2 and CXCL1 release from brain endothelial cells[J]. Int J Mol Sci, 2017,18(5): Pii: E1000
[19] Chastain E M, Duncan D S, Rodgers J M, et al. The role of antigen Presenting cells in multiple sclerosis[J]. Biochimica Et Biophysica Acta, 2011, 1812(2):265

相似文献/References:

[1]苟 芸,黄国伟,陈 爽,等.同型半胱氨酸对小鼠成神经瘤细胞毒性作用研究[J].天津医科大学学报,2015,21(03):6.
 GOU Yun,HUANG Guo-wei,CHEN Shuang,et al.Neurotoxicity of homocysteine on mouse N2a neuroblastoma cells[J].Journal of Tianjin Medical University,2015,21(05):6.
[2]苟 芸,黄国伟,陈 爽,等. 同型半胱氨酸对小鼠成神经瘤细胞毒性作用研究[J].天津医科大学学报,2015,21(01):6.
 GOU Yun,HUANG Guo-wei,CHEN Shuang,et al.Neurotoxicity of homocysteine on mouse N2a neuroblastoma cells[J].Journal of Tianjin Medical University,2015,21(05):6.
[3]麻仕利,王 伟,梁 蓉.同型半胱氨酸代谢关键酶基因多态性与单纯收缩期高血压关系的初步研究[J].天津医科大学学报,2016,22(02):93.
 MA Shi-li,WANG Wei,LIANG Rong.Preliminary study on the relationship between the gene polymorphisms of homocysteine metabolism-related enzymes and isolated systolic hypertension[J].Journal of Tianjin Medical University,2016,22(05):93.
[4]刘先锋,张 晶,丛洪良.血浆同型半胱氨酸水平与传统冠心病危险因素关系及对冠心病进展的作用[J].天津医科大学学报,2016,22(04):343.
[5]徐西子,董昭杰,马向红.血同型半胱氨酸水平与冠心病慢性心衰严重程度的相关性分析[J].天津医科大学学报,2017,23(03):221.
 XU Xi-zi,DONG Zhao- jie,MA Xiang-hong.Correlation of severity of chronic heart failure with plasma homocysteine level[J].Journal of Tianjin Medical University,2017,23(05):221.
[6]崔 鹏,杨建立.奥卡西平治疗的精神分裂症兴奋激越患者的效果及对血清Hcy的影响[J].天津医科大学学报,2019,25(01):66.
 CUI Peng,YANG Jian-Li.Effect of oxcarbazepine on patients with schizophrenia and excitement and its effect on serum Hcy[J].Journal of Tianjin Medical University,2019,25(05):66.

备注/Memo

备注/Memo:
作者简介 张宇(1982-),男,主治医师,博士,研究方向:老年医学;通信作者:王林,E-mail: wang lin@medmail.com.cn。
更新日期/Last Update: 2018-09-30