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解放军总医院医学创新研究部、国家老年疾病临床医学研究中心(解放军总医院)、解放军总医院第六医学中心心血管病医学部
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中华老年多器官疾病杂志编辑委员会
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创刊人 王士雯
总编辑 范利
副总编辑 陈韵岱
执行主编 叶大训
编辑部主任 王雪萍
ISSN 1671-5403
CN 11-4786
创刊时间 2002年
出版周期 月刊
邮发代号 82-408
友情链接
李丽雅,刘玉猛,张永,张新胜,杨雪艳,刘英华.嗜黏蛋白阿克曼菌对高脂饲料诱导的肥胖ApoE基因敲除小鼠血脂代谢及炎症因子的影响[J].中华老年多器官疾病杂志,2022,21(10):780~785
嗜黏蛋白阿克曼菌对高脂饲料诱导的肥胖ApoE基因敲除小鼠血脂代谢及炎症因子的影响
Effects of Akkermansia mucinophila on lipid metabolism and inflammatory factors in obese ApoE-/-mice induced by high-fat diet
投稿时间:2022-06-16  
DOI:10.11915/j.issn.1671-5403.2022.10.167
中文关键词:  嗜黏蛋白阿克曼菌  ApoE基因敲除小鼠  血脂代谢  炎症因子  肥胖
英文关键词:Akkermansia mucinophila  ApoE knockout mice  lipid metabolism  inflammatory factors  obesity This work was supported by the Medical Transformation Project of Chinese PLA General Hospital
基金项目:解放军总医院医学转化项目(ZH19012)
作者单位E-mail
李丽雅 中国人民解放军总医院第一医学中心营养科,北京 100853 liuyinghua77@163.comeffects 
刘玉猛 中国人民解放军总医院第一医学中心营养科,北京 100853 liuyinghua77@163.comeffects 
张永 中国人民解放军总医院第一医学中心营养科,北京 100853 liuyinghua77@163.comeffects 
张新胜 中国人民解放军总医院第一医学中心营养科,北京 100853 liuyinghua77@163.comeffects 
杨雪艳 中国人民解放军总医院第一医学中心营养科,北京 100853 liuyinghua77@163.comeffects 
刘英华 中国人民解放军总医院第一医学中心营养科,北京 100853 liuyinghua77@163.comeffects 
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中文摘要:
      目的 观察嗜黏蛋白阿克曼(AKK)对高脂饲料喂养的肥胖ApoE基因敲除(ApoE-/-)小鼠血脂代谢及炎症因子相关指标的影响。方法 选取健康SPF级雄性C57BL/6J及ApoE-/- 4周龄小鼠,均给予高脂饲料喂养。喂养6周后,选取高于C57BL/6J小鼠平均体质量10%的ApoE-/-小鼠20只,随机编号,奇数为模型组(n=10),偶数为AKK干预组(n=10),C57BL/6J小鼠作为对照组(n=10)。对照组与模型组小鼠灌胃不含AKK的甘油制剂,AKK干预组灌胃含1×109CFU AKK的甘油制剂。每日灌胃1次,每次0.1ml。灌胃4周后,称量小鼠空腹体质量,采集血清及附睾脂肪组织。检测血清甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)等血脂代谢指标水平,白细胞介素(IL)-1、IL-6、IL-8、IL-10、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)及单核细胞趋化蛋白-1(MCP-1)等炎症因子指标水平。称量附睾脂肪组织质量,苏木精-伊红(HE)染色观察小鼠附睾脂肪组织细胞形态及大小,测量脂肪组织细胞平均面积。采用SPSS 26.0统计软件进行数据分析。多组间比较采用单因素方差分析。结果 灌胃4周后,与模型组相比,AKK干预组小鼠空腹体质量、附睾脂肪组织质量及体脂百分比均有下降趋势,但差异无统计学意义(P>0.05);AKK干预组血脂代谢指标TG[(0.85±0.17)和(1.65±0.15)、(1.08±0.09)mmol/L]及LDL-C[(3.20±0.85)和(6.47±0.87)、(4.89±0.56)mmol/L]均显著低于模型组及对照组,HDL-C[(919.89±116.19)和(433.59±183.85)、(721.11±222.70)mmol/L]显著高于模型组及对照组,TC[(3.00±0.64)和(5.12±0.71)mmol/L]显著低于模型组,差异均有统计学意义(均P<0.05);AKK干预组炎症因子指标IL-1[(74.10±25.28)和(191.42±31.36)、(123.91±25.29)pg/ml]、IL-6[(63.10±9.53)和(100.76±11.42)、(77.76±8.20)pg/ml]、IL-8[(64.34±10.36)和(104.59±8.46)、(82.64±11.79)pg/ml]、CRP[(88.85±24.33)和(172.53±25.41)、(122.72±22.08)ng/ml]、TNF-α[(372.30±47.05)和(672.13±66.18)、(509.97±54.50)pg/ml]及MCP-1[(11.90±1.58)和(25.18±2.03)、(18.59±2.11)pg/ml]均显著低于模型组及对照组,差异均有统计学意义(均P<0.05),IL-10有升高趋势,但3组比较差异无统计学意义(P>0.05)。HE染色观察显示,AKK干预组较模型组小鼠附睾脂肪组织细胞平均面积[(330.45±55.84)和(879.58±36.74)μm2)]显著减小(P<0.05),形态规整,单个视野下脂肪细胞数量明显增多。结论 AKK可改善高脂饲料喂养的肥胖ApoE-/-小鼠的血脂异常,并降低肥胖ApoE-/-小鼠血清炎症因子水平。
英文摘要:
      Objective To observe the effects of Akkermansia muciniphila (AKK) on lipid metabolism and inflammatory factors in ApoE knockout (ApoE-/-) mice fed with high-fat diet. Methods Healthy SPF male C57BL/6J and ApoE-/- mice (4 weeks old) were selected and fed with high-fat diet. Six weeks later, 20 ApoE-/- mice with an average weight higher than 10% of that of C57BL/6J mice were selected and numbered randomly, and those with odd number were divided into the model group (n=10) and those with even number into the AKK intervention group (n=10). And another 10 C57BL/6J mice served as control group. The mice in the control group and the model group were intragastrically administrated with glycerol preparation without AKK, and those out of the AKK intervention group were given glycerol preparation containing 1×109CFU AKK, 0.1 ml each time, once per day. After intragastric administration for 4 weeks, fasting body weight was measured. Serum and epididymal adipose tissues were collected from each group. Serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-1 (IL-1), IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected. The weight of epididymal adipose tissue was weighed, and the morphology was observed after HE staining to calculate the average size of epididymal adipose tissue cells. SPSS statistics 26.0 was used for data analysis. One-way analysis of variance was used for comparison among multiple groups. Results After 4 weeks of intragastric administration of AKK, the fasting body weight, epididymal fat weight and body fat percentage were decreased in the AKK intervention group than the model group, though the differences not significant (P>0.05). The AKK intervention group had significantly lower TG (0.85±0.17 vs 1.65±0.15 and 1.08±0.09 mmol/L) and LDL-C levels (3.20±0.85 vs 6.47±0.87 and 4.89±0.56 mmol/L), and obviously higher HDL-C (919.89±116.19 vs 433.59±183.85 and 721.11±222.70 mmol/L) when compared with the model group and the control group (all P<0.05). The TC level was notably lower in the intervention group than the model group (3.00±0.64 vs 5.12±0.71 mmol/L, P<0.05). For the inflammatory factors, the levels of IL-1 (74.10±25.28 vs 191.42±31.36 and 123.91±25.29 pg/ml), IL-6 (63.10±9.53 vs 100.76±11.42 and 77.76±8.20 pg/ml), IL-8 (64.34±10.36 vs 104.59±8.46 and 82.64±11.79 pg/ml), CRP (88.85±24.33 vs 172.53±25.41 and 122.72±22.08 ng/ml), TNF-α (372.30±47.05 vs 674.53±62.18 and 509.97±54.50 pg/ml) and MCP-1 (11.90±1.58 vs 25.18±2.03 and 18.59±2.11 pg/ml) in the AKK group were remarkably lower than those in the model group and control group (all P<0.05). The IL-8 level was in a trend of increasing, but no statistical differences were seen among the 3 groups (P>0.05). HE staining showed that the average area of epididymal adipocytes was significantly smaller in the AKK intervention group than the model group (330.45±55.84 vs 879.58±36.74 μm2, P<0.05), and regular cell morphology and increased number of adipocytes in a single field of vision were also observed. Conclusion AKK improves dyslipidemia and reduces serum inflammatory factors in obese ApoE-/- mice fed with high-fat diet.
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