间歇低氧暴露上调肥胖小鼠胃Ghrelin、下丘脑GHSR表达

杨璐瑶; 付鹏宇; 唐舒宁; 朱镕鑫; 龚丽景

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间歇低氧暴露上调肥胖小鼠胃Ghrelin、下丘脑GHSR表达

首发时间：2020-02-28

杨璐瑶 ^{1
2}
杨璐瑶（1998-），女
付鹏宇 ² 唐舒宁 ² 朱镕鑫 ³ 龚丽景 ¹
龚丽景，女，硕导

1、北京体育大学中国运动与健康研究院，北京 100084
2、北京体育大学运动人体科学学院，北京 100084
3、上海体育科学研究所，上海 200030

摘要：目的：通过观察4周间歇低氧暴露对肥胖小鼠胃组织Ghrelin、Goat和下丘脑GHSR含量的变化，以明确低氧对胃组织Ghrelin-GHSR通路的影响机制。方法：将30只离乳C57BL/6J小鼠，随机分为普通对照组（C，n=8）和高脂膳食组（HD，n=22）。HD组饲喂8周高脂饲料建立肥胖模型，将肥胖模型建立成功的16只HD组小鼠其随机分为肥胖对照组（OB）和肥胖低氧组（H）。H组进行4周低氧暴露（氧浓度为11.2%），8 h/天，6次/周。干预结束后取血清、胃、下丘脑，检测血清TG、TC、GLU、总Ghrelin水平，RT-PCR测定胃组织Ghrelin和下丘脑GHSR-1a mRNA相对表达水平，HE染色法观察胃组织形态，免疫组化法测定胃组织Ghrelin和Goat的平均光密度值，WB测定胃组织Ghrelin、Goat 和下丘脑 GHSR-1a 蛋白表达水平。结果：低氧干预2周后，OB组的体重显著高于C组（P<0.01）；4周后，OB组体重显著高于C组（P<0.01）和H组（P<0.05）。干预期间，小鼠摄食量无显著变化。OB组GLU、TC、TG水平显著高于C组（GLU为8.53±0.81 mmol/L、TC为2.03±0.10 mg/dL、TG为0.29±0.02 mmol/L）；低氧暴露干预4周后，H组GLU（8.06±1.31mmol/L）、TC（3.90±0.31 mg/dL）水平显著低于OB组。H组血清Ghrelin（0.40±0.02mmol/L）水平显著高于OB组（0.30±0.01mmol/L）。OB组胃组织Ghrelin mRNA（0.28±0.12）相对表达量显著低于H组（0.41±0.18），下丘脑 GHSR-1a mRNA（0.28±0.14）水平极显著低于C组（1.00±0.13）。H组胃底腺主细胞规律、密集、均匀分布。H组胃组织Ghrelin（0.29±0.03）和Goat（0.29±0.03）的平均光密度值、下丘脑GHSR-1a（1.66±0.15）、胃组织Ghrelin（1.39±0.20）和Goat（1.31±0.09）蛋白含量显著高于OB组（0.26±0.02，0.22±0.02，1.14±0.08，0.82±0.16，1.16±0.28）。结论：4周低氧暴露可显著上调肥胖小鼠胃组织Ghrelin、Goat和下丘脑GHSR-1a的表达水平，降低肥胖机体的血糖和体重，改善肥胖对机体的不良影响。

关键词：低氧暴露肥胖胃组织下丘脑 Ghrelin-GHSR通路

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Intermittent Hypoxia Exposure Upregulates Gastric Ghrelin, Hypothalamus GHSR Of Obese Mice

YangLuyao ^{1
2}
杨璐瑶（1998-），女
FuPengyu ² TangShuning ² ZhuRongxin ³ GongLijing ¹
龚丽景，女，硕导

1、China Institute of Sports and Health of Beijing Sport University, Beijing, 100084
2、College of Human Sport Science, Beijing Sport University, Beijing, 100084
3、Shanghai Institute of Sports Science, Shanghai, 200030

Abstract：In this paper,the changes of gastric Ghrelin、Goat and hypothalamus GHSR content of obese mice were observed to explore the effect mechanism of 4 weeks intermittent hypoxia exposure on Ghrelin-GHSR pathway in gastric tissues. Thirty C57BL/6J male mice were randomly divided into control group (C, n=8) and high fat diet group (HD, n=22, fed with high fat diet). Sixteen HD mice with successful obesity model were randomly divided into obese control group (OB) and obese hypoxia group (H, 11.2% oxygen concentration, 8 h/day, 6 times/week), n=8, after 8 weeks. The TC, TG, GLU and total Ghrelin levels in serum were tested; the gastric Ghrelin mRNA expressions and hypothalamus GHSR-1a mRNA were tested by RT-PCR; gastric tissue morphology was observed by HE staining and the average optical density of Ghrelin and Goat in gastric tissue was measured by Immunohistochemistry; the protein expressions of GHSR-1a in hypothalamus tissue, Ghrelin and Goat in gastric tissue were detected by WB after 4 weeks of intervention. The body weight of group OB was obviously higher than group C (P<0.01) after 2 weeks of hypoxia intervention; the body weight of group OB was significantly higher than group C (P<0.01) and H (P<0.05) after 4 weeks. The food intakes of mice had no significant difference. The GLU (10.21±1.81 mmol/L)、TC(4.52±0.33 mg/dL) and TG(0.34±0.03 mmol/L)in group OB were significantly higher than group C(8.53±0.81 mmol/L、2.03±0.10 mg/dL、0.29±0.02 mmol/L); GLU(8.06±1.31mmol/L)、TC(3.90±0.31 mg/dL) in group H were obviously lower than group OB after 4 weeks hypoxia intervention. The total serum Ghrelin(0.40±0.02mmol/L) in group H was significantly higher than group OB(0.30±0.01mmol/L). The Ghrelin mRNA(0.28±0.12) relative expression in gastric tissue of group OB was evidently lower than group H(0.41±0.18), and GHSR-1a mRNA (0.28±0.14) in hypothalamus was very significantly lower than group C(1.00±0.13). Group H had a regular, dense and uniform distribution of gastric fundus gland main cells. The average optical density of Ghrelin(0.29±0.03) and Goat(0.29±0.03) in gastric tissue as well as the protein contents of hypothalamus GHSR-1a(1.66±0.15) and gastric Ghrelin(1.39±0.20), Goat(1.31±0.09) of group H were evidently higher than group OB(0.26±0.02, 0.22±0.02, 1.14±0.08, 0.82±0.16, 1.16±0.28). Four weeks hypoxia exposure can increase the expression of Ghrelin, Goat in gastric tissue and GHSR-1a in hypothalamus of obese mice significantly, reduce blood sugar and body weight of obese mice also improve adverse effects of obesity on mice.

Keywords： Hypoxic exposure Obesity Gastric tissue Hypothalamus Ghrelin-GHSR pathway

基金：

1. 北京市大学生创新创业训练计划项目（2019CISH04）

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杨璐瑶，付鹏宇，唐舒宁，等. 间歇低氧暴露上调肥胖小鼠胃Ghrelin、下丘脑GHSR表达[EB/OL]. 北京：中国科技论文在线 [2020-02-28]. https://www.paper.edu.cn/releasepaper/content/202002-158.

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论文编号	202002-158
论文题目	间歇低氧暴露上调肥胖小鼠胃Ghrelin、下丘脑GHSR表达
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