Ghrelin对兔激素性股骨头缺血性坏死中VEGF的影响

doi:10.6040/j.issn.1671-7554.0.2014.033

摘要/Abstract

摘要： 目的观察Ghrelin对兔激素性股骨头缺血性坏死（sANFH）中血管内皮生长因子（VEGF）表达的影响。方法选择24周龄以上雄性新西兰兔34只，随机分为正常组（n=8）和造模组（n=26）。造模采用马血清联合甲基强的松龙的方法，每组各取4只行股骨头磁共振及病理组织学检查，明确造模是否成功。将造模组造模成功的20只随机分为对照组（n=10）和Ghrelin干预组（n=10），正常组剩余4只纳入空白组。Ghrelin干预组连续2周耳缘静脉注射Ghrelin[25μg/（kg·d）]，对照组连续2周耳缘静脉注射相同剂量生理盐水；2周后空气栓塞法处死动物，收集标本，行股骨头组织形态学观察、RT-PCR法检测股骨头组织中VEGF的表达。结果对照组股骨头病理组织学检查可见骨小梁广泛稀疏、大部分断裂，脂肪细胞可见融合现象；Ghrelin干预组可见骨小梁稀疏，偶见断裂；脂肪细胞较多并轻度肥大，在骨髓中所占比例多于正常组，未见融合现象。RT-PCR法检测结果显示，对照组和Ghrelin干预组VEGF表达均高于空白组（P<0.05）；同时Ghrelin干预组VEGF表达明显高于对照组（P<0.05）。结论 Ghrelin可促进激素性缺血性股骨头坏死组织中VEGF mRNA的表达，从而改善坏死股骨头组织微循环，进一步改善激素性缺血性股骨头坏死的进程。

关键词: 激素性缺血性股骨头坏死, 血管内皮生长因子, 兔, 磁共振, Ghrelin

Abstract: Objective To observe the effect of Ghrelin on the expression of vascular endothelial growth factor (VEGF) in steroid-induced avasular necrosis of the femoral head in rabbits. Methods A total of 34 male New-Zealand rabbits which aged more than 24 weeks were divided into normal group (n=8) and model group (n=26). Models of steroid-induced avascular necrosis of femoral head were induced by horse serum combined with hormone methylprednisolone. After that, 4 rabbits were selected from each group randomly to determine with MRI and histopathological examinations if the modeling was successful. The 20 successfully modeled rabbits were divided into control group (n=10) and Ghrelin intervention group (n=10), and the remaining 4 in the normal group were classified as blank group. Rabbits in Ghrelin intervention group received Ghrelin injection (25 μg/kg·d) for 2 weeks, and rabbits in control group were given the same dose of saline for 2 weeks. Samples were collected after the animals were sacrificed. The histomorphology of femoral head was examined, and VEGF mRNA level was detected with Real-time PCR. Results The control group displayed extensive sparse and broken trabecula, and adipocytes were fused. The Ghrelin intervention group showed occasionally broken sparse trabecula. The adipocytes were slightly hypertrophic but not fused, with a higher proportion in the marrow than in the control group. VEGF mRNA expression was higher in Ghrelin intervention group and controlgroup than in blank group (P<0.05), and it was higher in the Ghrelin intervention group than in the control group (P<0.05). Conclusion Ghrelin can up-regulate the expression of VEGF in steroid-induced avasular necrosis of femoral head in rabbits, and improve the microcirculation and progression of femoral head.

Key words: Avascular necrosis of the femoral head, Ghrelin, Rabbits, Vascular Endothelial Growth Factor, Magnetic Resonance Imaging

中图分类号:

R493

黄来刚, 崔宝娟, 王晓红, 王道清, 曾凡硕, 孙敏, 刘本玲, 孙强三. Ghrelin对兔激素性股骨头缺血性坏死中VEGF的影响[J]. 山东大学学报（医学版）, 2014, 52(9): 48-53.

HUANG Laigang, CUI Baojuan, WANG Xiaohong, WANG Daoqing, ZENG Fanshuo, SUN Min, LIU Benling, SUN Qiangsan. Effect of Ghrelin on the VEGF expression in steroid-induced avascular necrosis of the femoral head in rabbits[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 48-53.

参考文献

[1] 尤全喜.专家谈股骨头坏死[M]. 北京:中医古籍出版社,2003:10-12.
[2] Cummings D E, Shannon M H.Roles for ghrelin in the regulation of appetite and body weight[J]. Arch Surg, 2003, 138(4):389-396.
[3] Horvath, Diano S, Sotonyi P, et al. Minireview:ghrelin and the regulation of energy balance-a hypothalamic per-spective[J]. Endocrinology, 2001,142(10):4163-4169.
[4] Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach[J]. Nature, 1999, 402(6762):656-660.
[5] Date Y, Kojima M, Hosoda H, et al.Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans[J]. Endocrinology, 2000, 141(11):4255-4261.
[6] Gualillo O, Caminos J E, Kojima M, et al. Gender and gonadal influences on ghrelin mRNA levels in rat stomach[J]. Eur J Endocrinol, 2001, 144(6):687-690.
[7] Bowers C Y. Unnatural growth hormone-releasing peptide begets natural ghrelin[J]. J Clin Endocrinol Metab, 2001, 86(4):1464-1469.
[8] Date Y, Murakami N, Kojima M,et al.Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats[J]. Biochem Biophys Res Commun, 2000, 275(2):477-480.
[9] Sakata I, Nakamura K, Yamazaki M, et al. Ghrelin-producing cells exist as two types of cells, closed- and opened-type cells, in the rat gastrointestinal tract[J]. Peptides, 2002, 23(3):531-536.
[10] Delhanty P J, van der Eerden B C, van Leeuwen J P.Ghrelin and bone[J]. Biofactors, 2014, 40(1):41-48.
[11] Liang Q H, Liu Y, Wu S S, et al. Ghrelin inhibits the apoptosis of MC3T3-E1 cells through ERK and AKT signaling pathway [J]. Toxicol Appl Pharmacol, 2013, 272(3):591-597.
[12] Fukushima N, Hanada R, Teranishi H, et al. Ghrelin directly regulates bone formation [J]. J Bone Miner Res, 2005, 20(5):790-798.
[13] Maccarinelli G, Sibilia V, Torsello A, et al. Ghrelin regulates proliferation and differentiationof osteoblastic cells[J]. J Endocrinol, 2005, 184(1):249-256.
[14] Fukushima N, Hanada R, Teranishi H, et al. Ghrelin directly regulates bone formation[J]. J Bone Miner Res, 2005, 20(5):790-798.
[15] Maccarinelli G, Sibilia V, Torsello A,et al.Ghrelin reg-ulates proliferation and differentiation of osteoblastic cells [J]. J Endocrinol, 2005, 184(1):249-256.
[16] Larsson B, Norlén P, Lindström E, et al. Effects of ECL cell extracts and granule/vesicle-enriched fractions from rat oxyntic mucosa on cAMP and IP(3) in rat osteoblast-like cells[J]. Regul Pept, 2002, 106(1-3):13-18.
[17] Kerachian M A, Harvey E J, Cournoyer D, et al. Avascular necrosis of the femoral head: vascular hypotheses [J]. Endothelium, 2006, 13(4):237-244.
[18] Feng L, Wu H, E L, et al.Effects of vascular endothelial growth factor 165 on bone tissue engineering [J]. PLoS ONE, 2013, 8(12):82945.
[19] Turner N, Grose R. Fibroblast growth factor signalling:from development to cancer [J]. Nat Rev Cancer, 2010, 10(2):116-129.
[20] Horner A, Bishop N J, Bord S, et al. Immunolocalisation of vascular endothelial growth factor (VEGF) in human neonatal growth plate cartilage[J]. J Anat, 1999, 194(4):519-524.
[21] Petersen W, Pufe T, Zantop T, et al. Expression of VEGFR-1 and VEGFR-2 in degenerative Achilles tendons [J]. Jorthop Res, 2004(420):286-291.
[22] Pufe T, Claassen H, Scholz-Ahrens K E, et al. Influence of estradiol on vascular endothelial growth factor expression in bone: a study in Göttingen miniature pigs and human osteoblasts [J]. Calcif Tissue Int, 2007, 80(3):184-191.
[23] Vadasz Z, Misselevich I, Normman D, et al. Localization of vascular endothelial growth factor during the early reparative phase of the rats' vessels deprivation-induced osteonecrosis of the femoral heads [J]. Exp Mol Pathol, 2004, 77(2):145-148.

相关文章 15

[1]	王韶卿刘毅慧付婷婷成金勇刘强. 肝癌³¹磷磁共振波谱数据的分类[J]. 山东大学学报(医学版), 2209, 47(6): 42-46.
[2]	黄方康瑞吴春林. VEGFC、NF-κBp65及Survivin在鼻咽癌中的表达及临床意义[J]. 山东大学学报(医学版), 2209, 47(6): 83-.
[3]	吴强,何泽鲲,刘琚,崔晓萌,孙双,石伟. 基于机器学习的脑胶质瘤多模态影像分析[J]. 山东大学学报 (医学版), 2020, 1(8): 81-87.
[4]	王玉红,张丽红,王林省,陈月芹,王彦辉,王皆欢,李传福. 消化道颗粒细胞瘤的影像学表现[J]. 山东大学学报（医学版）, 2017, 55(8): 66-70.
[5]	窦瑞欣,薛敏娜,李国华. 基于VTK实现三维重建在胆囊管变异中的诊断价值[J]. 山东大学学报（医学版）, 2017, 55(7): 84-88.
[6]	樊彦伟,严冬雪,招友. 富氢水对兔腰椎间盘退变的影响[J]. 山东大学学报（医学版）, 2017, 55(3): 38-42.
[7]	许玉军,柳明,何祥萌,李成利. 1.0T开放型磁共振引导经皮穿刺¹²⁵I放射性粒子植入治疗晚期胰腺癌[J]. 山东大学学报（医学版）, 2017, 55(2): 21-25.
[8]	王光彬. MRI在凶险性前置胎盘诊断中的价值[J]. 山东大学学报（医学版）, 2016, 54(9): 7-9.
[9]	沙莎,Chowdhury Sumon Rahman,陈丽,何芹,张婧,范珊珊,孙磊. 利拉鲁肽对高脂诱导肥胖小鼠瘦素、脂肪分布及含量的影响[J]. 山东大学学报（医学版）, 2016, 54(8): 22-27.
[10]	高萌,孙建民,蒋振松,崔新刚. MRI在布氏杆菌脊柱炎诊断中的应用价值[J]. 山东大学学报（医学版）, 2016, 54(6): 27-30.
[11]	董金叶,林祥涛,曹金凤,吴勇,赵慧,谢辉辉,肖连祥. 16~42周胎儿脊髓颈膨大发育的MRI分析[J]. 山东大学学报（医学版）, 2016, 54(5): 74-78.
[12]	张湛,许相丰,刘海东,王玮. MRI在宫颈癌T分期中的诊断价值[J]. 山东大学学报（医学版）, 2016, 54(5): 70-73.
[13]	徐延杰,崔谊,李红霞,史文琦,李福艳,王建震,曾庆师. X线照射对U87胶质瘤多细胞球体MMP-2活性及Cho/Cr的影响[J]. 山东大学学报（医学版）, 2016, 54(4): 6-10.
[14]	刁晓君,陈春富,李聪聪,张颖博,李婴婴. 多发性硬化患者原发性头痛的特征及发病情况[J]. 山东大学学报（医学版）, 2016, 54(4): 42-45.
[15]	李冉冉,张鹏飞,袁冰,房菲菲, 韩明勇. 乳腺癌MCF-7细胞分泌的血管内皮生长因子诱导血管内皮细胞免疫功能抑制[J]. 山东大学学报（医学版）, 2016, 54(2): 38-43.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed