重组人生长激素对慢性束缚应激诱导小鼠抑郁样行为的改善作用及其机制

doi:10.13481/j.1671-587X.20250407

摘要/Abstract

摘要：

目的观察重组人生长激素（rh-GH）对慢性束缚应激（CRS）小鼠抑郁样行为的影响，探讨其可能的作用机制。方法采用CRS法建立抑郁症动物模型，45只小鼠分为对照组（不建模，n=15）和CRS模型组（建模，n=30），通过糖水偏爱实验（SPT）检测2组小鼠糖水偏好率，悬尾实验（TST）检测2组小鼠悬尾静止时间，旷场实验（OFT）检测2组小鼠在5 min内总的移动距离和在中心区域停留的时间。CRS小鼠随机分为CRS模型+生理盐水组和CRS模型+rh-GH组，每组10只，CRS模型+生理盐水组小鼠注射生理盐水，CRS模型+rh-GH组小鼠皮下注射rh-GH 1个月，在干预前后采集2组小鼠外周血，检测2组小鼠血清中生长激素（GH）和胰岛素样生长因子Ⅰ（IGF-Ⅰ）水平，行为学实验结束后，取2组小鼠海马组织检测组织中突触蛋白1（SYN-1）表达水平。结果与对照组比较，CRS模型组小鼠体质量明显降低（P<0.01），SPT中糖水偏好率明显降低（P<0.01），TST中不动时间明显延长（P<0.01），在OFT中小鼠总移动距离差异无统计学意义（P>0.05），而在中心区停留的时间明显缩短（P<0.05）。与对照组比较，CRS模型组小鼠血清中GH和IGF-Ⅰ水平明显降低（P<0.01）。与CRS模型+生理盐水组比较，CRS模型+rh-GH组小鼠在SPT中的糖水偏好率明显升高（P<0.01），在TST中的不动时间明显缩短（P<0.05），在OFT中总的移动距离差异无统计学意义（P>0.05），在中心区域停留的时间明显增加（P<0.01）。与CRS模型+生理盐水组比较，CRS模型+rh-GH组小鼠血清中GH和IGF-Ⅰ水平明显升高（P<0.01），小鼠海马组织中SYN-1水平明显升高（P<0.05）。结论 rh-GH对CRS诱导的小鼠抑郁样行为具有改善作用，其机制可能与调节GH/IGF-Ⅰ轴及增加海马组织SYN-1蛋白表达有关。

关键词: 抑郁样行为, 重组人生长激素, 胰岛素样生长因子Ⅰ, 突触蛋白1, 慢性束缚应激

Abstract:

Objective To observe the effects of recombinant human growth hormone （rh-GH） on depressive-like behavior in mice with chronic restraint stress （CRS）， and to discuss its possible mechanism. Methods The CRS method was used to establish an animal model of depression； a total of 45 mice were didided into control group （non-modeled， n=15）， and CRS model group （modeled， n=30） the sucrose preference test （SPT） was used to detect the sucrose preference rate of the mice； the tail suspension test （TST） was used to detect the immobility time of the mice； the open field test （OFT） was used to detect the total moving distance of the mice within 5 min and the time spent in the central area. The CRS mice were randomly divided into CRS model+saline group and CRS model+rh-GH group（n=10）； the mice in CRS model+saline group were injected with normal saline； the mice in CRS model+rh-GH group were subcutaneously injected with rh-GH daily for 1 month； the peripheral blood of the mice was collected before and after intervention to detect the expression levels of growth hormone （GH） and insulin-like growth factor Ⅰ （IGF-Ⅰ） proteins in serum； after all behavioral experiments， the hippocampus tissue was taken to detect the expression level of synapsin-1 （SYN-1） protein in the tissue of the mice. Results Compared with control group， the body weight of the mice in CRS model group was significantly decreased （P<0.01）， the sucrose preference rate in SPT was significantly decreased （P<0.01）， the immobility time in TST was significantly prolonged （P<0.01）； in OFT， the total moving distance of mice showed no significant change （P>0.05）， while the time spent in the central area was significantly shortened （P<0.05）. Compared with control group， the expression levels of GH and IGF-Ⅰ proteins in serum of the mice in CRS model group were significantly decreased （P<0.01）. Compared with CRS model+saline group， the sucrose preference rate in SPT of the mice in CRS model+rh-GH group was significantly increased （P<0.01）， the immobility time in TST was significantly shortened （P<0.05）， the total moving distance in OFT showed no significant difference （P>0.05）， and the time spent in the central area was significantly increased （P<0.01）. Compared with model+saline group， the expression levels of GH and IGF-I proteins in serum of the mice in CRS model+rh-GH group were significantly increased （P<0.01）. Compared with model group， the expression level of SYN-1 protein in hippocampus tissue of mice in drug-treated model group was significantly increased （P<0.05）. Conclusion rh-GH has ameliorative effects on depressive-like behavior induced by chronic restraint stress in mice， and its mechanism may be associated with regulation of the GH/IGF-Ⅰ axis and increased expression of SYN-1 in hippocampus tissue.

Key words: Depressive-like behavior, Recombinant human growth hormone, Insulin-like growth factor Ⅰ, Synapsin-1, Chronic restraint stress

中图分类号:

R749.4

李建芳,李莹华,连雅雯,陈晓伟. 重组人生长激素对慢性束缚应激诱导小鼠抑郁样行为的改善作用及其机制[J]. 吉林大学学报(医学版), 2025, 51(4): 914-920.

Jianfang LI,Yinghua LI,Yawen LIAN,Xiaowei CHEN. Effect of recombinant human growth hormone on depression-like behaviors induced by chronic restraint stress in mice and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 914-920.

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Group	Sucrose preferencee(η/%)	lmmobility time(t/s)	Total dstance traveled(l/cm)	Time spent in center area(t/s)
CRS model+saline	0.60±0.02	103.47±7.50	1 537.05±66.23	58.94±2.48
CRS model+rh-GH	0.81±0.03^*	79.70±4.56^**	1 481.75±101.48	74.59±2.43^*