Chinese Journal of Tissue Engineering Research ›› 2017, Vol. 21 ›› Issue (32): 5209-5214.doi: 10.3969/j.issn.2095-4344.2017.32.021
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Chen Yu-feng, Yang Hui-lin, Zou Jun
Received:
2017-06-09
Online:
2017-11-18
Published:
2017-11-15
Contact:
Zou Jun, M.D., Associate chief physician, Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
About author:
Chen Yu-feng, Studying for master’s degree, Department of Orthopedics, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
Supported by:
the General Project of National Natural Science Foundation of China, No. 81572183
CLC Number:
Chen Yu-feng, Yang Hui-lin, Zou Jun. Ghrelin effects on the growth hormone release, osteoblast proliferation and bone growth[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(32): 5209-5214.
2.1 Ghrelin与机体各类激素的免疫调节 Ghrelin是生长激素促分泌素受体的内源性配体,是一个有28个氨基酸的肽,其中在3-丝氨酸残基被辛酰化,因此也被称为新型生长激素释放酰化肽。人类ghrelin和鼠ghrelin有2个氨基酸的不同。Ghrelin可以增加人和动物促皮质素、皮质酮以及促进脑下垂体生长激素的分泌(图1)。但ghrelin促进促皮质素、皮质酮分泌的机制还不清楚,有学者研究了ghrelin对促肾上腺皮质激素释放因子和精氨酸加压素,结果显示ghrelin与细胞共培养4 h可以增加精氨酸加压素mRNA的表达,但并未检测到促肾上腺皮质激素释放因子mRNA表达的变化,说明ghrelin主要通过下丘脑精氨酸加压素促进促皮质素的分泌[9]。也有研究分析了ghrelin对脑下垂体血清生长激素浓度和生长激素mRNA水平的影响,结果显示ghrelin可以增加血清生长激素浓度,ghrelin剂量越大,血清生长激素浓度越高,反之血清生长激素浓度则减少。但ghrelin对血清生长激素浓度的影响随时间而减少,ghrelin对生长激素mRNA水平无影响,也就是说ghrelin可以促进生长激素释放,但不能促进其生长激素合成[4]。"
Ghrelin及其受体表达于多种免疫细胞,可以多种内分泌方式调节免疫细胞的功能。Ghrelin可以改善胸腺功能,抑制炎性细胞因子的产生。在炎性疾病患者中ghrelin的水平升高,这可能是对炎症的一种保护性反应。与此同时,ghrelin还可以通过刺激生长激素分泌间接调节免疫系统的功能。通过调节饮食和体质量等从而改变ghrelin的分泌,这可能成为增强机体免疫功能的一种方法。以往研究最多的是ghrelin的调节生长激素分泌及能量代谢、进胃酸分泌,调节胃肠运动等作用,已经有研究表明葡萄糖对ghrelin合成与分泌有显著的抑制作用[10-11]。安振梅等[12]选取10例肥胖的2型糖尿病患者,研究糖负荷和馒头负荷对肥胖和非肥胖的2型糖尿病者血清ghrelin的影响及二者与胰岛素、血糖的关系,结果显示能量摄入相似的情况下,2型糖尿病患者ghrelin对葡萄糖和馒头餐的反应不同;空腹ghrelin与空腹胰岛素负相关、与胰岛素敏感指数正相关。同样有研究显示空腹血糖水平和胰岛素抵抗是导致青少年血ghrelin水平变化的独立危险因素,ghrelin水平降低可能是青少年糖代谢异常的保护因素[13-16]。脂类对ghrelin的作用比较复杂,有动物实验研究分析表明,脂质灌注诱导了肝脏和外周的胰岛素抵抗,高胰岛素血症,而不是游离脂肪酸,降低了大鼠循环ghrelin水平[17]。严光等[18]通过对54例需要禁食的患者进行临床研究发现,血浆ghrelin浓度变化与禁食前患者的脂肪含量有关,体脂含量越高,ghrelin升高出现的时间越晚。同时随着禁食时间的延长,ghrelin的分泌会逐渐增加。提示禁食状态下,ghrelin的分泌变化与禁食前脂肪组织与体质量的比值及禁食时间有关。大量文献证实,胃切除后空腹ghrelin明显上升,对血糖的调控明显改善。推测胰岛素抵抗改善的机制可能与ghrelin的调节有关[19-21]。同样研究发现一定浓度的ghrelin促进胰岛在高葡萄糖诱导下的胰岛素分泌,经ghrelin预处理24 h后该作用更为显著[22]。Ghrelin增加大鼠胰岛内前胰岛素原mRNA的表达,促进胰岛素合成。为了解ghrelin缓解胰岛素抵抗的机制,有实验选取骨骼肌细胞作为研究对象,着重研究胰岛素抵抗的骨骼肌细胞质钙离子的变化及ghrelin对钙离子稳态的维持作用,以及其引起的细胞内葡萄糖转运蛋白的变化,结果发现ghrelin可通过影响钙离子改善胰岛素抵抗、加强细胞内葡萄糖转运蛋白的作用。Ghrelin可能是联系内分泌与骨骼生长的重要物质之一[23],见表1。"
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