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通过提高雌二醇水平补充钙对去卵巢大鼠减少骨质流失影响的代谢组学和生理学分析

Metabolomics and physiological analysis of the effect of calcium supplements on reducing bone loss in ovariectomized rats by increasing estradiol levels.

作者信息

Mao Hongmei, Wang Wenjun, Shi Lili, Chen Chen, Han Chao, Zhao Jinpeng, Zhuo Qin, Shen Shi, Li Yan, Huo Junsheng

机构信息

National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing, 100050, China.

Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

出版信息

Nutr Metab (Lond). 2021 Jul 23;18(1):76. doi: 10.1186/s12986-021-00602-y.

DOI:10.1186/s12986-021-00602-y
PMID:34301294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8305954/
Abstract

BACKGROUND

Data from the 2010-2012 Chinese National Nutrition and Health Survey showed that the vast majority of postmenopausal women in China had dual deficiencies in calcium and estrogen.

OBJECTIVE

This study aimed to clarify whether calcium supplementation alleviated bone loss caused by calcium restriction combined with estrogen deficiency in rats.

METHODS

Forty-eight female rats aged 9 weeks were assigned to 4 groups and fed a low-calcium diet: sham-operated (SHAM-LC), ovariectomized (OVX-LC), and ovariectomized rats treated with 750 mg/kg (OVX-LC-M) or 2800 mg/kg CaCO (OVX-LC-H). CaCO or distilled water was administered orally for 13 weeks. Bone mineral density (BMD) and histomorphometry of the femur, serum biochemical parameters, and serum metabolites were analyzed.

RESULTS

The OVX-LC rats showed a significant increase in body weight and serum levels of lipid markers, a significant decrease in serum estradiol, calcium, phosphorus, and 25(OH)D levels, and deterioration of the femur. At 750 mg/kg and 2800 mg/kg, CaCO reduced the deterioration of trabecular bone and increased the trabecular area percentage (Tb.Ar %) and BMD of the femur. Serum estradiol levels increased in a dose-dependent manner after CaCO supplementation (p < 0.01). The administration of 2800 mg/kg CaCO decreased serum triglyceride and high-density lipoprotein levels (p < 0.05) and decreased the levels of the bone turnover markers osteocalcin, N-telopeptide of type I collagen and β-crosslaps. The results of the metabolomics analysis showed that the glycerophospholipid metabolism pathway was closely related to calcium supplementation, and more DG (44:6 n3), LysoPC (22:2) and PE (P-34:3) and less Cer (d43:0) and PE-NMe2 (46:3) were produced.

CONCLUSIONS

The results clearly indicated that calcium supplementation was beneficial for decreasing bone loss in OVX-LC rats. The present study is the first to show that calcium supplementation increased the estradiol content in OVX-LC rats, and the effect of calcium on bone loss may be partially attributed to the increase in the estrogen level that subsequently induced the changes in metabolite levels, eventually increasing the bone mineral density to a relatively higher level to reduce bone deterioration.

摘要

背景

2010 - 2012年中国国家营养与健康调查数据显示,中国绝大多数绝经后女性存在钙和雌激素双重缺乏。

目的

本研究旨在明确补钙是否能减轻钙限制联合雌激素缺乏所致大鼠的骨质流失。

方法

将48只9周龄雌性大鼠分为4组,给予低钙饮食:假手术组(SHAM - LC)、卵巢切除组(OVX - LC)、卵巢切除且给予750 mg/kg碳酸钙治疗组(OVX - LC - M)以及卵巢切除且给予2800 mg/kg碳酸钙治疗组(OVX - LC - H)。口服碳酸钙或蒸馏水13周。分析股骨的骨密度(BMD)、组织形态计量学、血清生化参数及血清代谢产物。

结果

OVX - LC大鼠体重及血清脂质标志物水平显著升高,血清雌二醇、钙、磷及25(OH)D水平显著降低,股骨状况恶化。给予750 mg/kg和2800 mg/kg碳酸钙可减轻小梁骨恶化,增加股骨小梁面积百分比(Tb.Ar %)及骨密度。补钙后血清雌二醇水平呈剂量依赖性升高(p < 0.01)。给予2800 mg/kg碳酸钙可降低血清甘油三酯及高密度脂蛋白水平(p < 0.05),并降低骨转换标志物骨钙素、I型胶原N - 端肽及β - 交联羧基末端肽水平。代谢组学分析结果表明,甘油磷脂代谢途径与补钙密切相关,产生了更多的二酰甘油(44:6 n3)、溶血磷脂酰胆碱(22:2)和磷脂酰乙醇胺(P - 34:3),而神经酰胺(d43:0)和N - 甲基磷脂酰乙醇胺(46:3)减少。

结论

结果明确表明,补钙有利于减少OVX - LC大鼠的骨质流失。本研究首次表明,补钙可增加OVX - LC大鼠的雌二醇含量,钙对骨质流失的影响可能部分归因于雌激素水平的升高,随后雌激素诱导代谢物水平发生变化,最终将骨密度提高到相对较高水平以减轻骨质恶化。

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