山东大学学报 (医学版) ›› 2017, Vol. 55 ›› Issue (12): 7-12.doi: 10.6040/j.issn.1671-7554.0.2017.150
卿立,何天祎,乔婧婷,崔晨,侯新国,陈丽
QING Li, HE Tianyi, QIAO Jingting, CUI Chen, HOU Xinguo, CHEN Li
摘要: 目的 探讨富半胱氨酸蛋白61(Cyr61)在肥胖小鼠脂肪组织中的表达、分布及其与脂肪慢性炎症的关系。 方法 4周龄雄性C57BL/6小鼠30只,随机分为普通饮食组(NC组)和高脂喂养组(HFD组),每组15只。HFD组给予60%脂肪含量高脂饲料喂养,构建肥胖小鼠模型,NC组给予普通饲料喂养。造模成功后测量小鼠体脂含量,通过在腹腔注射葡萄糖进行葡萄糖耐量试验(IPGTT)检测糖耐量和血脂,取睾周脂肪检测Cyr61的表达及分布,并检测脂肪组织肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的mRNA表达量。 结果 HFD组脂质量、体内脂肪含量明显增加,糖耐量减低,血清总胆固醇和低密度脂蛋白胆固醇较正常高(P<0.05)。HFD组脂肪组织TNF-α、IL-6表达上调(P<0.05),Cyr61在HFD组脂肪组织中蛋白及mRNA水平均增加(P<0.05),且主要分布于脂肪组织基质中。 结论 Cyr61在肥胖小鼠脂肪组织表达明显增加,主要定位于脂肪组织基质中,且与炎症因子表达具有一致性,提示其可能与慢性炎症的发生相关。
中图分类号:
[1] | Bi Y, Xu Y, Ning G. Prevalence of diabetes in Chinese adults-reply[J]. JAMA, 2014, 311(2): 200-201. |
[2] | Hotamisligil GS. Inflammation and metabolic disorders[J]. Nature, 2006, 444(7121): 860-867. |
[3] | Chawla A, Nguyen KD, Goh YP. Macrophage-mediated inflammation in metabolic disease[J]. Nat Rev Immunol, 2011, 11(11): 738-749. |
[4] | Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease[J]. J Clin Invest, 2011, 121(6): 2111-2117. |
[5] | Shu CJ, Benoist C, Mathis D. The immune systems involvement in obesity-driven type 2 diabetes[J]. Semin Immunol, 2012, 24(6): 436-442. |
[6] | Obrien TP, Yang GP, Sanders L, et al. Expression of cyr61, a growth factor-inducible immediate-early gene[J]. Mol Cell Biol, 1990, 10(7): 3569-3577. |
[7] | Lin J, Huo R, Xiao L, et al. A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis[J]. Arthritis Rheumatol, 2014, 66(1): 49-59. |
[8] | Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance[J]. Science, 1993, 259(5091): 87-91. |
[9] | Li P, Lu M, Nguyen MT, et al. Functional heterogeneity of CD11c-positive adipose tissue macrophages in diet-induced obese mice[J]. J Biol Chem, 2010, 285(20): 15333-15345. |
[10] | Kintscher U, Hartge M, Hess K, et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance[J]. Arterioscler Thromb Vasc Biol, 2008, 28(7): 1304-1310. |
[11] | Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance[J]. Nat Rev Endocrinol, 2012, 8(12): 709-716. |
[12] | Lumeng CN, Maillard I, Saltiel AR. T-ing up inflammation in fat[J]. Nat Med, 2009, 15(8): 846-847. |
[13] | Winer S, Chan Y, Paltser G, et al. Normalization of obesity-associated insulin resistance through immunotherapy[J]. Nat Med, 2009, 15(8): 921-929. |
[14] | Lau LF, Nathans D. Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells[J]. EMBO J, 1985, 4(12): 3145-3151. |
[15] | Obrien TP, Lau LF. Expression of the growth factor-inducible immediate early gene cyr61 correlates with chondrogenesis during mouse embryonic development[J]. Cell Growth Differ, 1992, 3(9): 645-654. |
[16] | Jay P, Berge-Lefranc JL, Marsollier C, et al. The human growth factor-inducible immediate early gene, CYR61, maps to chromosome 1p[J]. Oncogene, 1997, 14(14): 1753-1757. |
[17] | Leng E, Malcolm T, Tai G, et al. Organization and expression of the Cyr61 gene in normal human fibroblasts[J]. J Biomed Sci, 2002, 9(1): 59-67. |
[18] | 王志敏, 丛雅琴, 马立宁, 等. Cyr61基因与慢性粒细胞白血病的相关性研究[J]. 山东大学学报(医学版), 2009, 47(10): 94-97. WANG Zhimin, CONG Yaqin, MA Lining, et al. Correlation between Cyr61 and chronic myelogenousleukemis[J]. Journal of Shandong University(Health Sciences), 2009, 47(10): 94-97. |
[19] | 牛志宏, 高德轩, 丁森泰, 等. Cyr61、CTGF、NOV、WISP-1基因在肾癌中的表达[J]. 山东大学学报(医学版), 2008, 46(7): 701-703. NIU Zhihong, GAO Dexuan, DING Sentai, et al. Expression of Cyr61, CTGF, NOV and WISP-1 in renal cell carcinoma[J]. Journal of Shandong University(Health Sciences), 2008, 46(7): 701-703. |
[20] | Tong X, Okelly J, Xie D, et al. Cyr61 suppresses the growth of non-small-cell lung cancer cells via the beta-catenin-c-myc-p53 pathway[J]. Oncogene, 2004, 23(28): 4847-4855. |
[21] | Matsumae H, Yoshida Y, Ono K, et al. CCN1 knockdown suppresses neointimal hyperplasia in a rat artery balloon injury model[J]. Arterioscler Thromb Vasc Biol, 2008, 28(6): 1077-1083. |
[22] | Athanasopoulos AN, Schneider D, Keiper T, et al. Vascular endothelial growth factor(VEGF)-induced up-regulation of CCN1 in osteoblasts mediates proangiogenic activities in endothelial cells and promotes fracture healing[J]. J Biol Chem, 2007, 282(37): 26746-26753. |
[23] | Zhang Q, Wu J, Cao Q, et al. A critical role of Cyr61 in interleukin-17-dependent proliferation of fibroblast-like synoviocytes in rheumatoid arthritis[J]. Arthritis Rheum, 2009, 60(12): 3602-3612. |
[24] | Koon HW, Shih DQ, Hing TC, et al. Substance P induces CCN1 expression via histone deacetylase activity in human colonic epithelial cells[J]. Am J Pathol, 2011, 179(5): 2315-2326. |
[25] | Koon HW, Zhao D, Xu H, et al. Substance P-mediated expression of the pro-angiogenic factor CCN1 modulates the course of colitis[J]. Am J Pathol, 2008, 173(2): 400-410. |
[26] | Lantz M, Vondrichova T, Parikh H, et al. Overexpression of immediate early genes in active Graves' ophthalmopathy[J]. J Clin Endocrinol Metab, 2005, 90(8): 4784-4791. |
[27] | Lin J, Zhou Z, Huo R, et al. Cyr61 induces IL-6 production by fibroblast-like synoviocytes promoting Th17 differentiation in rheumatoid arthritis[J]. J Immunol, 2012, 188(11): 5776-5784. |
[28] | 徐京京, 赵琳, 张晓莉, 等. 类风湿关节炎患者血清CCN1水平变化及意义[J]. 山东医药, 2016, 56(21): 58-59. XU Jingjing, ZHAO Lin, ZHANG Xiaoli, et al. Changes and significance of serum CCN1 in patients with rheumatoid arthritis[J]. Shandong Med J, 2016, 56(21): 58-59. |
[29] | Zhu X, Xiao L, Huo R, et al. Cyr61 is involved in neutrophil infiltration in joints by inducing IL-8 production by fibroblast-like synoviocytes in rheumatoid arthritis[J]. Arthritis Res Ther, 2013, 15(6): 187. |
[30] | Schipper HS, Prakken B, Kalkhoven E, et al. Adipose tissue-resident immune cells: key players in immunometabolism[J]. Trends Endocrinol Metab, 2012, 23(8): 407-415. |
[31] | Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance[J]. J Clin Invest, 2006, 116(7): 1793-1801. |
[1] | 张媛 李英敏 冯月秋 常彩云 潘华伟 王束玫. 血清脂联素水平与肥胖、胰岛素抵抗的关系探讨[J]. 山东大学学报(医学版), 2209, 47(6): 124-. |
[2] | 张凤,吴哲,徐俊,刘玉兰. 6例非酒精性脂肪性肝病小鼠肠道B细胞的变化[J]. 山东大学学报 (医学版), 2022, 60(9): 67-73. |
[3] | 邬雨洁,张明泉,纪永利,赵璐,王越,陈沙沙. 寒痉汤及其拆方对寒凝证高血压大鼠血清炎症因子、血管内皮功能及纤维化的影响[J]. 山东大学学报 (医学版), 2022, 60(6): 10-18. |
[4] | 孙继业,王紫欧,孙晓伟,李洪涛. 中药熏蒸联合体外冲击波对72例髋关节撞击综合征临床疗效、血清炎症因子水平的影响[J]. 山东大学学报 (医学版), 2022, 60(4): 76-81. |
[5] | 韩晓婷,于霞,董来慧,纳莉,牛艳玲,赵君利. 月见草油对肥胖型不孕女性代谢及肠道菌群的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 48-54. |
[6] | 李涵,付婷婷,张磊,延冰,孙涛,郭峰,尹晓. 过氧化物酶增殖物激活受体γ激动剂对24例肥胖症患者米色脂肪细胞分化的影响[J]. 山东大学学报 (医学版), 2020, 1(9): 8-13. |
[7] | 扈艳雯,王志媛,郁万江,赵蕙琛,韩合理,徐志鹏,马红,张玉超,刘元涛. 52例肥胖患者脂肪分布与代谢综合征及糖代谢指标的相关性[J]. 山东大学学报 (医学版), 2020, 1(8): 101-106. |
[8] | 胡昭,王强. 新型冠状病毒感染相关性肾损伤[J]. 山东大学学报 (医学版), 2020, 58(3): 26-31. |
[9] | 杨张杰,王宇欣,陈冬梅,赵帅,虎娜,马良宏,马会明. 枸杞籽油对小鼠睾丸支持细胞衰老模型的抗炎作用[J]. 山东大学学报 (医学版), 2020, 58(12): 15-22. |
[10] | 余雪源,张硕,燕芳芳,苏德振. 采用清肺排毒汤联合西药43例与单用西药46例的新型冠状病毒肺炎临床疗效比较[J]. 山东大学学报 (医学版), 2020, 58(12): 47-53. |
[11] | 黄凤艳,许俐,刘平,王志萍. 会阴裂伤在孕前BMI与产后盆底肌功能障碍关联性中的中介作用[J]. 山东大学学报 (医学版), 2019, 57(2): 99-104. |
[12] | 王敏,王春花,刘鸿丽,何志良,崔薇薇,王磊,刘杰军. 男性儿童瘦素抵抗对成年后健康状况的影响[J]. 山东大学学报 (医学版), 2018, 56(10): 114-118. |
[13] | 张素萍,王泽,周亚丽, 李敬,路西兰,柏宏伟,石玉华. 来曲唑治疗不同体质量指数多囊卵巢综合征患者的临床效果[J]. 山东大学学报(医学版), 2017, 55(5): 81-85. |
[14] | 闫松鹤,高立芬,赵伟,王燕. 人牙根尖乳头细胞抑制人单核细胞THP-1活化及其分子机制[J]. 山东大学学报(医学版), 2017, 55(3): 49-53. |
[15] | 杨延军,梁静,李芳,杜令席. 常山酮对小鼠子宫内膜异位症巨噬细胞极化的调控作用[J]. 山东大学学报(医学版), 2016, 54(9): 26-31. |
|