心理应激对雌性小鼠胃泌素、雌激素及其胃食管炎症因子的影响

doi:10.3877/cma.j.issn.2095-8765.2020.04.003

中华胃食管反流病电子杂志 ›› 2020, Vol. 07 ›› Issue (04) : 207 -212. doi: 10.3877/cma.j.issn.2095-8765.2020.04.003

论著

心理应激对雌性小鼠胃泌素、雌激素及其胃食管炎症因子的影响

阿孜古丽·阿力木江¹, 买买提·依斯热依力²^,^†(

), 王婧¹, 艾克拜尔·艾力³, 陆萍¹, 克力木·阿不都热依木²

^1. 830001　乌鲁木齐，新疆维吾尔自治区人民医院妇产科门诊
^2. 830001　乌鲁木齐，新疆维吾尔自治区人民医院自治区普外微创研究所；830001　乌鲁木齐，新疆维吾尔自治区人民医院临床医学研究中心
^3. 830001　乌鲁木齐，新疆维吾尔自治区人民医院自治区普外微创研究所

收稿日期:2020-02-16 出版日期:2020-11-05
通信作者: 买买提·依斯热依力
基金资助:
?????新疆维吾尔自治区人民医院院内项目［项目名称：慢性心理应激对雌性小鼠卵巢功能的作用机制研究(20190113)

Effects of psychological stress on gastrin and estrogen levels and it's role in esophagitis of female mice

Aziguli·Alimujiang¹, Maimaiti·Yisireyili²^,^†(), Jing Wang¹, Aikebaier·Aili³, Ping Lu¹, Kelimu·Abudureyimu²

^1. Department of Obstetrics and Gynecology Clinic, Research Center for Clinical Medecine, People's Hospital of Xinjiang Uygur Autonomous Region, 830001, China.
^2. Research Institute of General and Minimally Invasive Surgery, Research Center for Clinical Medecine, People's Hospital of Xinjiang Uygur Autonomous Region, 830001, China.

Received:2020-02-16 Published:2020-11-05
Corresponding author: Maimaiti·Yisireyili

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阿孜古丽·阿力木江, 买买提·依斯热依力, 王婧, 艾克拜尔·艾力, 陆萍, 克力木·阿不都热依木. 心理应激对雌性小鼠胃泌素、雌激素及其胃食管炎症因子的影响[J]. 中华胃食管反流病电子杂志, 2020, 07(04): 207-212.

Aziguli·Alimujiang, Maimaiti·Yisireyili, Jing Wang, Aikebaier·Aili, Ping Lu, Kelimu·Abudureyimu. Effects of psychological stress on gastrin and estrogen levels and it's role in esophagitis of female mice[J]. Chinese Journal of Gastroesophageal Reflux Disease(Electronic Edition), 2020, 07(04): 207-212.

目的

探讨心理应激对雌性小鼠胃泌素、雌二激素及其食管炎症因子的影响。

方法

20只8周龄，雌性SPF级昆明小鼠随机分为心理应激组和正常对照组，每组各10只。两组小鼠单只饲养在自由进食水的鼠笼内，心理应激组小鼠每天在自制式束缚器中限制活动2 h，持续14 d；对照组小鼠不进行束缚。实验14 d后，行H&E染色并在光镜下观察食管粘膜组织病理学改变，进一步通过实时定量PCR和酶联免疫吸附法检测血液中和食管粘膜组织中氧化应激（Nox-4）及炎症因子（IL-1β、IL-8、TNF-α）等指标的mRNA表达量；酶联免疫吸附法检测两组胃泌素和雌二醇激素在血液中的水平。

结果

心理应激小鼠血液中胃泌素和雌二醇激素水平较对照组更低，两者比较的差异有统计学意义（t=4.265，5.622；P＜0.05）；心理应激组小鼠食管粘膜层可见基底细胞增生，中性粒细胞、嗜酸性粒细胞及浆细胞浸润反应和炎症性改变。心理应激组小鼠食管粘膜炎症细胞评分较对照组更高，两者比较的差异有统计学意义（t=7.512，P＜0.05）。心理应激组小鼠食管粘膜组织氧化应激指标（Nox-4）的mRNA表达量以及血液中的水平较对照组更高，两者比较的差异有统计学意义（t=5.546，6.013；P＜0.05）。心理应激组食管粘膜组织炎症因子（IL-1β、IL-8及TNF-α）的mRNA表达量以及血液中的水平较对照组更高，两者比较的差异有统计学意义（t=7.124，5.876，6.832，2.317，4.681，8.105；P＜0.05）。

结论

心理应激引起胃泌素和雌二醇水平降低，促进食管粘膜炎症性损伤。

关键词: 心理应激, 胃泌素, 雌二醇, 食管炎

Objective

To investigate the effects of psychological stress on gastrin and estrogen in female mice and its role on inflammation.

Methods

Eight week old female SPF Kunming mice were randomly divided into stress group (n=10) and control group (n=10). The mice in the stress group were restricted for 2 hours each day in the self-made bonder, and lasted for 14 days. Then, the mice in two groups were freely allowed to drink and eat in the same environment. H&E staining was performed and histopathological changes of esophageal mucosa were observed under light microscope. Furthermore, the mRNA expressions of oxidative stress (Nox-4) and inflammatory factors (IL-1β, IL-8, TNF-α)in esophageal mucosa and their content in blood were detected by real-time quantitative PCR and ELISA.

Results

After 14 days of stress period, the levels of gastrin and estradiol in the blood of stress mice were significantly lower than control group(P＜0.05); basal cell proliferation, neutrophil, eosinophil and plasma cell infiltration and inflammatory changes were observed in the mucous layer of esophagus in stress group, and the score of esophageal mucositis in the stress group was significantly higher than control group (P＜0.05); the expression of Nox-4 mRNA and its blood levels in stress group was significantly increased (P＜0.05); RT-PCR and ELISA showed that the mRNA expression levels and blood levels of IL-1β, IL-8, TNF-α were significantly increased (P＜0.05).

Conclusion

The stress induces the decrease of gastrin and estradiol in female mice, and further lead to esophageal inflammation.

Key words: psychological stress, gastrin, estradiol, esophagitis

表1 实时定量RT-PCR引物序列及产物长度

引物	上游引物（5'-3'）	下游引物（5'-3'）	bp
Nox-4	ACTCCTTGGGTCAGCACTGG	GTTCCTGTCCAGTTGTCTTCG	160
IL-1β	AACCTGCTGGTGTGTGACGTTC	CAGCACGAGGCTTTTTTGTTGT	78
IL-8	CGGCAATGAAGCTTCTGTAT	CCTTGAAACTCTTTGCCTCA	224
TNF-α	AGGCTGCCCCGACTACGT	GACTTTCTCCTGGTATGAGATAGCAAA	70
β-actin	TATTGGCAACGAGCGGTTC	ATGCCACAGGATTCCATACCC	75

表1 实时定量RT-PCR引物序列及产物长度

引物	上游引物（5'-3'）	下游引物（5'-3'）	bp
Nox-4	ACTCCTTGGGTCAGCACTGG	GTTCCTGTCCAGTTGTCTTCG	160
IL-1β	AACCTGCTGGTGTGTGACGTTC	CAGCACGAGGCTTTTTTGTTGT	78
IL-8	CGGCAATGAAGCTTCTGTAT	CCTTGAAACTCTTTGCCTCA	224
TNF-α	AGGCTGCCCCGACTACGT	GACTTTCTCCTGGTATGAGATAGCAAA	70
β-actin	TATTGGCAACGAGCGGTTC	ATGCCACAGGATTCCATACCC	75

图1 两组小鼠血清激素水平比较（每组n=10，^aP＜0.05 vs 正常组）

图2 两组食管粘膜组织H & E染色

图3 两组食管组织Nox-4的表达水平比较（n=10，^aP＜0.05 vs 正常组）

图4 两组食管组织炎症因子mRNA表达水平的比较（n=10，^aP＜0.05 vs 正常组）

图5 两组血清炎症因子水平比较（n=10，^aP＜0.05 vs 正常组）

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