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慢性心理应激对大鼠睾丸细胞老化的影响及糖皮质激素受体的作用研究
Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process
- 陆军军医大学学报 2024年46卷第24期 页码：2698-2706
- 作者机构：
1.400038 重庆，陆军军医大学(第三军医大学)军事预防医学系军事毒理学教研室
2.401520 重庆，重庆市合川区疾病预防控制中心
- 作者简介：
[邹鹏，E-mail: julinlaotou@tmmu.edu.cnZOU Peng, E-mail: julinlaotou@tmmu.edu.cn
- 基金信息：国家自然科学基金青年科学基金(82003429)
DOI：10.16016/j.2097-0927.202406014
中图分类号： R322.64;R363.21;R395.2收稿：2024-06-07，
修回：2024-07-15，
纸质出版：2024-12-30
- 稿件说明：
移动端阅览
杨彬伟, 孙磊, 凌曦, 等. 慢性心理应激对大鼠睾丸细胞老化的影响及糖皮质激素受体的作用研究[J]. 陆军军医大学学报, 2024,46(24):2698-2706.
Binwei YANG, Lei SUN, Xi LING, et al. Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process[J]. Journal of Army Medical University, 2024, 46(24): 2698-2706.
杨彬伟, 孙磊, 凌曦, 等. 慢性心理应激对大鼠睾丸细胞老化的影响及糖皮质激素受体的作用研究[J]. 陆军军医大学学报, 2024,46(24):2698-2706. DOI： 10.16016/j.2097-0927.202406014.
Binwei YANG, Lei SUN, Xi LING, et al. Effects of chronic psychological stress on testicular cell senescence in rats and role of glucocorticoid receptor in the process[J]. Journal of Army Medical University, 2024, 46(24): 2698-2706. DOI： 10.16016/j.2097-0927.202406014.
摘要
目的
2
探讨慢性心理应激对大鼠睾丸细胞老化的影响以及糖皮质激素受体(glucocorticoid receptor
GR)在上述损害中的作用。
方法
2
将32只4~6周龄雄性SD大鼠(体质量120~140 g)按随机数字表法平均分为4组: 二甲基亚砜(dimethyl sulfoxide
DMSO)组、米非司酮(mifepristone
RU486)组、慢性不可预知温和应激(chronic unpredictable mild stress
CUMS)组和CUMS+RU486组。DMSO组采用DMSO皮下注射
剂量为0.5 mL/(kg/d); RU486组采用米非司酮皮下注射
剂量为1 mg/(kg/d); CUMS组采用CUMS单独造模处理; CUMS+RU486组在CUMS造模的同时采用RU486皮下注射
剂量为1 mg/(kg/d)
以上4组均连续处理42 d。造模结束后采用动物行为学试验评估大鼠心理应激状况。计算机辅助精子分析(computer-aided sperm analysis
CASA)系统检测各组大鼠精子密度。酶联免疫法吸附试验法(enzyme-linked immuno sorbent assay
ELISA)检测血清皮质酮(corticosterone
CORT)、性激素和炎症因子浓度。分别采用丙二醛(malondialdehyde
MDA)、H
2
O
2
、NAD
+
/NADH和ATP试剂盒检测各组动物睾丸组织MDA、H
2
O
2
、NAD
+
/NADH和ATP的含量。Western blot检测睾丸组织β-gal、p16和GR等蛋白表达水平。透射电镜观察精原细胞线粒体结构。
结果
2
与DMSO组比较
CUMS组精子密度、血清睾酮(testosterone
T)、黄体生成素(luteinizing hormone
LH)和卵泡刺激素(follicle stimulating hormone
FSH)浓度显著下降而血清CORT和雌二醇(estradiol
E
2
)浓度升高(
P
均
<
0.001)
血清促炎因子IL-6和TNF-α浓度升高而抗炎因子IL-10浓度降低(
P
均
<
0.05)
睾丸组织ATP含量和NAD
+
/NADH比值降低而MDA和H
2
O
2
含量升高(
P
均
<
0.05)
睾丸细胞老化标志物β-gal、p16和GR蛋白表达水平显著升高(
P
均
<
0.01)
精原细胞线粒体呈现肿胀及空泡化改变。与CUMS组比较
CUMS+RU486组精子密度和血清睾酮水平显著升高
β-gal、p16和GR蛋白表达水平显著降低(
P
均
<
0.05)。
结论
2
慢性心理应激诱导大鼠睾丸损害
表现为精子密度和血清睾酮水平下降
其机制可能与GR介导的细胞老化有关。
Abstract
Objective
2
To investigate the effect of chronic psychological stress on testicular cell senescence in rats and the role of glucocorticoid receptor (GR) in the process.
Methods
2
Thirty-two male SD rats (4~6 weeks old
weighing 120~140 g) were randomly assigned into dimethyl sulfoxide (DMSO) group
mifepristone (RU486) group
chronic unpredictable mild stress (CUMS) group
and CUMS+RU486 group.DMSO of 0.5 ml/(kg·d) was injected subcutaneously into the rats of DMSO group.After the rats of the CUMS group were exposed to CUMS
mifepristone of 1 mg/(kg·d) was given to the rats of the RU486 group and CUMS+RU486 group.All the above 4 groups were inflicted for 42 consecutive days.After modeling
the psychological stress status of rats was evaluated with animal behavioral experiments.Computer-aided sperm analysis (CASA) system was used to detect sperm density.ELISA was employed to measure the serum levels of corticosterone (CORT)
sex hormones and inflammation factors.The contents of malondialdehyde (MDA)
H
2
O
2
NAD
+
/NADH and ATP in the testicular tissues were tested with corresponding reagent kits.Western blotting was utilized to detect protein levels of β-gal
p16
and GR in testicular tissue
and transmission electro
n microscopy was used to observe mitochondrial structure of spermatogenic cells.
Results
2
Compared with the DMSO group
the sperm density
serum levels of testosterone (T)
luteinizing hormone (LH) and follicle stimulating hormone (FSH) were decreased while those of CORT and estradiol (E
2
) were increased in the CUMS group (all
P
<
0.001).Serum pro-inflammatory factors IL-6 and TNF-α concentrations were increased while anti-inflammatory factor IL-10 concentration was decreased in the CUMS group than the DMSO group (all
P
<
0.05).And
ATP content and NAD
+
/NADH ratio were decreased while MDA and H
2
O
2
levels were elevated in testicular tissues in the CUMS group (all
P
<
0.05).Moreover
the protein levels of testicular cell aging markers β-gal
p16 and GR were significantly enhanced in the CUMS group (all
P
<
0.01)
accompanied by swelling and vacuolization of mitochondrial structures in spermatogenic cells.RU486 treatment effectively improved sperm density and increased CORT level and down-regulated the testicular β-gal
p16 and GR protein level (all
P
<
0.05).
Conclusion
2
Chronic psychological stress induces testicular damage in rats
presenting declines in sperm density and CORT level
which is possibly associated with GR-mediated cell senescence.
关键词
Keywords
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