骨鈣素通過抑制脂肪組織炎癥改善肥胖小鼠胰島素敏感性
發(fā)布時間：2018-08-11 09:14
【摘要】：肥胖已經(jīng)威脅到人類的健康,成為了眾多疾病共同的危險因素,如心腦血管疾病,高血壓,高血脂,糖尿病等,這與肥胖導(dǎo)致的慢性低度炎癥反應(yīng)相關(guān),其中巨噬細胞向脂肪組織的浸潤在炎癥反應(yīng)及胰島素抵抗中發(fā)揮了重要作用,而巨噬細胞趨化蛋白1(MCP-1)則是導(dǎo)致巨噬細胞向脂肪組織浸潤的重要因素之一。眾多實驗研究都致力于探索出有效的途徑來減輕脂肪組織炎癥反應(yīng),從而改善胰島素抵抗,預(yù)防2型糖尿病的發(fā)生。骨鈣素,是由成骨細胞分泌的一種蛋白,它能促使骨轉(zhuǎn)化和骨合成,最新的研究發(fā)現(xiàn)它在調(diào)節(jié)糖及能量代謝方面也發(fā)揮了重要作用,從而能在一定程度上改善胰島素抵抗,然而其相關(guān)機制尚不明確,本研究對不同劑量骨鈣素對小鼠血糖、體脂量、胰島素水平及肥胖相關(guān)的炎癥反應(yīng)指標(biāo)等的影響作用及機制進行了深入的探討,有望進一步擴大骨鈣素的研究領(lǐng)域,同時在減輕肥胖相關(guān)的炎癥反應(yīng)方面獲得新的突破。本實驗選取C57BL/6小鼠,以高脂飲食喂養(yǎng)12周后,對肥胖小鼠每日腹腔注射骨鈣素(30ng/kg或3ng/kg),對照組以等體積的生理鹽水處理。測定各組小鼠體重、體脂、血清甘油三酯、游離脂肪酸變化;進行葡萄糖耐量試驗、胰島素耐量試驗;免疫組化染色觀察巨噬細胞向脂肪組織的浸潤程度及巨噬細胞標(biāo)志物CD68的蛋白表達量;實時熒光定量PCR檢測巨噬細胞趨化蛋白1(MCP-1)及CD68mRNA表達。通過本實驗研究,表明骨鈣素(30ng/kg或者3ng/kg)處理4周后,與生理鹽水處理的對照組相比,能有效降低高脂飲食小鼠的體重、體脂量、空腹胰島素水平,改善其糖耐量異常和胰島素抵抗。此外,在骨鈣素(30ng/kg)治療肥胖小鼠脂肪組織巨噬細胞的浸潤減少,脂肪組織中MCP-1與CD68mRNA表達明顯降低。該實驗表明長期高脂飲食會使小鼠體重及脂肪含量明顯增加,內(nèi)臟脂肪組織出現(xiàn)炎癥反應(yīng),產(chǎn)生了胰島素抵抗,二者存在一定的相關(guān)性。骨鈣素(30ng/kg)通過下調(diào)CD68和MCP-1的表達,抑制肥胖小鼠脂肪組織巨噬細胞聚集及MCP-1分泌,降低小鼠體重、體內(nèi)脂肪含量,改善了肥胖小鼠的胰島素敏感性。
[Abstract]:Obesity has threatened human health and become a common risk factor for many diseases, such as cardio-cerebrovascular disease, hypertension, hyperlipidemia, diabetes, and so on, which is associated with chronic low-grade inflammation caused by obesity. The infiltration of macrophages into adipose tissue plays an important role in inflammatory response and insulin resistance, and macrophage chemoattractant protein-1 (MCP-1) is one of the important factors leading to the infiltration of macrophages into adipose tissue. Many experimental studies have focused on finding effective ways to reduce inflammation in adipose tissue, improve insulin resistance and prevent type 2 diabetes. Osteocalcin, a protein secreted by osteoblasts that promotes bone transformation and bone synthesis, has been found to play an important role in regulating glucose and energy metabolism, thereby improving insulin resistance to some extent. However, the related mechanism of osteocalcin was not clear. The effects and mechanisms of different doses of osteocalcin on blood glucose, body fat, insulin level and inflammatory response indexes related to obesity in mice were studied. It is expected to further expand the research field of osteocalcin and make a new breakthrough in reducing the inflammatory response related to obesity. In this experiment, C57BL/6 mice were fed with high-fat diet for 12 weeks. The obese mice were given intraperitoneal injection of osteocalcin (30ng/kg or 3ng/kg) daily, and the control group was treated with normal saline of the same volume. Body weight, body fat, serum triglyceride, free fatty acid were measured, glucose tolerance test and insulin tolerance test were performed. The infiltration of macrophages into adipose tissue and the protein expression of macrophage marker CD68 were observed by immunohistochemical staining, and the expression of chemotactic protein 1 (MCP-1) and CD68mRNA in macrophages were detected by real-time fluorescence quantitative PCR. The results showed that after 4 weeks of treatment with 30ng/kg or 3ng/kg, compared with the control group treated with normal saline, the body weight, body fat and fasting insulin level of mice fed with high fat diet were significantly decreased, and compared with the control group treated with normal saline, osteocalcin (30ng/kg or 3ng/kg) could effectively reduce the body weight, body fat and fasting insulin level. Improve glucose tolerance and insulin resistance. In addition, osteocalcin (30ng/kg) treatment decreased the infiltration of macrophages in adipose tissue and the expression of MCP-1 and CD68mRNA in adipose tissue of obese mice. The results showed that long-term high-fat diet could significantly increase the body weight and fat content of mice, and the visceral adipose tissue appeared inflammatory reaction, which resulted in insulin resistance, and there was a certain correlation between them. Osteocalcin (30ng/kg) can down-regulate the expression of CD68 and MCP-1, inhibit macrophage aggregation and MCP-1 secretion in adipose tissue of obese mice, decrease body weight and fat content, and improve insulin sensitivity in obese mice.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R589.2;R587.1
本文編號：2176558
[Abstract]:Obesity has threatened human health and become a common risk factor for many diseases, such as cardio-cerebrovascular disease, hypertension, hyperlipidemia, diabetes, and so on, which is associated with chronic low-grade inflammation caused by obesity. The infiltration of macrophages into adipose tissue plays an important role in inflammatory response and insulin resistance, and macrophage chemoattractant protein-1 (MCP-1) is one of the important factors leading to the infiltration of macrophages into adipose tissue. Many experimental studies have focused on finding effective ways to reduce inflammation in adipose tissue, improve insulin resistance and prevent type 2 diabetes. Osteocalcin, a protein secreted by osteoblasts that promotes bone transformation and bone synthesis, has been found to play an important role in regulating glucose and energy metabolism, thereby improving insulin resistance to some extent. However, the related mechanism of osteocalcin was not clear. The effects and mechanisms of different doses of osteocalcin on blood glucose, body fat, insulin level and inflammatory response indexes related to obesity in mice were studied. It is expected to further expand the research field of osteocalcin and make a new breakthrough in reducing the inflammatory response related to obesity. In this experiment, C57BL/6 mice were fed with high-fat diet for 12 weeks. The obese mice were given intraperitoneal injection of osteocalcin (30ng/kg or 3ng/kg) daily, and the control group was treated with normal saline of the same volume. Body weight, body fat, serum triglyceride, free fatty acid were measured, glucose tolerance test and insulin tolerance test were performed. The infiltration of macrophages into adipose tissue and the protein expression of macrophage marker CD68 were observed by immunohistochemical staining, and the expression of chemotactic protein 1 (MCP-1) and CD68mRNA in macrophages were detected by real-time fluorescence quantitative PCR. The results showed that after 4 weeks of treatment with 30ng/kg or 3ng/kg, compared with the control group treated with normal saline, the body weight, body fat and fasting insulin level of mice fed with high fat diet were significantly decreased, and compared with the control group treated with normal saline, osteocalcin (30ng/kg or 3ng/kg) could effectively reduce the body weight, body fat and fasting insulin level. Improve glucose tolerance and insulin resistance. In addition, osteocalcin (30ng/kg) treatment decreased the infiltration of macrophages in adipose tissue and the expression of MCP-1 and CD68mRNA in adipose tissue of obese mice. The results showed that long-term high-fat diet could significantly increase the body weight and fat content of mice, and the visceral adipose tissue appeared inflammatory reaction, which resulted in insulin resistance, and there was a certain correlation between them. Osteocalcin (30ng/kg) can down-regulate the expression of CD68 and MCP-1, inhibit macrophage aggregation and MCP-1 secretion in adipose tissue of obese mice, decrease body weight and fat content, and improve insulin sensitivity in obese mice.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R589.2;R587.1
【參考文獻】
相關(guān)期刊論文 前5條
1 劉冬梅;劉建民;;骨鈣素對糖代謝的調(diào)控作用[J];中華骨質(zhì)疏松和骨礦鹽疾病雜志;2015年02期
2 戴小宇;滕華建;徐興全;姚堯;葛啟婷;蔣青;;骨鈣素調(diào)節(jié)糖代謝的研究進展[J];中國病理生理雜志;2013年05期
3 郭曉強;;骨鈣素:一種重要的能量代謝調(diào)節(jié)激素[J];生命科學(xué);2011年01期
4 李新;袁莉;李進;李海玲;程梭梭;;長期高脂喂養(yǎng)大鼠胰島功能改變與胰島炎癥反應(yīng)有關(guān)[J];中國病理生理雜志;2009年05期
5 崔麗娟;都健;;脂聯(lián)素與炎癥及胰島素抵抗關(guān)系的研究進展[J];國際內(nèi)分泌代謝雜志;2006年S1期
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