【摘要】：目的探討胰高血糖素樣肽1(GLP-1)受體激動(dòng)劑艾塞那肽對(duì)肥胖小鼠肝臟脂肪變性及肝功能的影響。方法將8周齡雄性C57BL/6J小鼠隨機(jī)分為普通飼料組(NG)和高脂飼料組(HG)喂養(yǎng)12周,HG組肥胖模型建模成功后再隨機(jī)分為高劑量艾塞那肽組〔H組,腹腔注射0.02μg/(g·d),高脂飼料喂養(yǎng)〕、低劑量艾塞那肽組〔L組,腹腔注射0.01μg/(g·d),高脂飼料喂養(yǎng)〕、生理鹽水對(duì)照組(NS組,腹腔注射等量生理鹽水,高脂飼料喂養(yǎng))、飲食干預(yù)組(D組,更換為普通飼料喂養(yǎng))、高脂對(duì)照組(M組,繼續(xù)高脂飼料喂養(yǎng))進(jìn)行干預(yù),干預(yù)4周;NG組繼續(xù)喂養(yǎng)4周。干預(yù)4周后分別測(cè)量各組小鼠的血清生化指標(biāo),包括血脂、肝功能、血糖(Glu)、尿酸(SUA)、胰島素(INS),計(jì)算胰島素抵抗指數(shù)(HOMA-IR),觀察體質(zhì)量變化情況,并取肝組織行HE染色,評(píng)估脂肪變性程度。結(jié)果治療4周后,NS組、M組小鼠體質(zhì)量均較治療前增加(P0.001):H、L、D組小鼠體質(zhì)量均較治療前降低,且H組小鼠體質(zhì)量降低較L組及D組明顯(P0.05)。H組、L組、M組、NS組丙氨酸氨基轉(zhuǎn)移酶(ALT)水平低于NG組(P0.05)。飲食治療和藥物治療都可降低三酰甘油(TG)和總膽固醇(TC)至正常水平〔NS組高于NG組(P0.05),NG組與H組、L組、D組的差異無統(tǒng)計(jì)學(xué)意義(P0.05)〕,但H組、L組和D組在TC、TG水平的組間差異無統(tǒng)計(jì)學(xué)意義(P0.05)。高劑量藥物治療存在SUA水平升高的風(fēng)險(xiǎn)〔H組SUA水平高于其余各組(P0.05)〕。門冬氨酸氨基轉(zhuǎn)移酶(AST)、Gly、HOMA-IR、脂肪酶(LIP)、淀粉酶(AMY)各組間差異無統(tǒng)計(jì)學(xué)意義(P0.05)。飲食治療和藥物治療均可改善肝組織的脂肪變性〔NS組脂肪變性評(píng)分高于NG組(P0.05),H、L、D組脂肪變性評(píng)分與NG組差異無統(tǒng)計(jì)學(xué)意義(P0.05)〕。結(jié)論高劑量GLP-1受體激動(dòng)劑能有效降低肥胖小鼠體質(zhì)量,但在改善血脂和肝細(xì)胞脂肪變性方面與飲食干預(yù)差別不大。
[Abstract]:Objective to investigate the effect of glucagon-like peptide 1 (GLP-1) receptor agonist Essena peptide on hepatic steatosis and liver function in obese mice. Methods 8-week-old male C57BL/6J mice were randomly divided into common diet group (NG) and high-fat diet group (HG) for 12 weeks. HG group was randomly divided into high-dose eseneptide group (H group, intraabdominal injection of 0.02 渭 g / g 路d), high-fat diet) and low-dose eseneptide group (L group, intraabdominal injection of 0.01 渭 g / g 路d), high-fat diet). Saline control group (NS group, intraabdominal injection of the same amount of normal saline, high-fat feed), diet intervention group (group D, replaced by ordinary feed), high-fat control group (group M, continue high-fat feed feeding) intervention for 4 weeks; The NG group was fed for 4 weeks. After 4 weeks of intervention, serum biochemical indexes, including blood lipid, liver function, blood glucose (Glu), uric acid (SUA), insulin (INS), insulin resistance index (HOMA-IR) were calculated, the changes of body mass were observed, and the liver tissues were stained with HE to evaluate the degree of steatosis. Results after 4 weeks of treatment, the body mass of mice in NS group and M group increased compared with that before treatment (P0.001): h, L, D group decreased body mass, and H group decreased significantly compared with L group and D group (P 0.05). The level of alanine aminotransferase (ALT) in NS group was lower than that in NG group (P 0.05). Diet therapy and drug treatment could reduce (TG) and total cholesterol (TC) of triacylglycerol to normal level (NS group was higher than NG group (P 0.05), NG group, H group, L group, D group had no significant difference (P 0.05), but H group, L group and D group had no significant difference in TC,TG level (P 0.05). There was a risk of increased SUA level in high dose drug therapy (SUA level in group H was higher than that in other groups (P 0.05). There was no significant difference in aspartate aminotransferase (AST), Gly,HOMA-IR, lipase (LIP), amylase (AMY) among groups (P 0.05). Diet therapy and drug treatment could improve steatosis of liver tissue (steatosis score in NS group was higher than that in NG group (P 0.05). There was no significant difference in steatosis score between group D and NG group (P 0.05). Conclusion High dose GLP-1 receptor agonist can effectively reduce the body mass of obese mice, but it is not different from diet intervention in improving blood lipid and hepatocytic steatosis.
【作者單位】： 四川大學(xué)華西醫(yī)院實(shí)驗(yàn)醫(yī)學(xué)科;四川大學(xué)華西醫(yī)院全科醫(yī)學(xué)科;四川大學(xué)華西醫(yī)院內(nèi)分泌代謝科;
【基金】：國家自然科學(xué)基金青年項(xiàng)目(No.81501800和No.81400811)資助
【分類號(hào)】：R589.2

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