Metrnl表达降低促进结直肠癌发生和发展

目的 探讨Metrnl与结直肠癌的关系及其在结直肠癌发生发展中的作用。方法 利用人体组织芯片分析结直肠癌和癌旁组织中Metrnl的表达与分布(n=30)。收集临床结直肠癌组织样本15例,利用实时定量多聚酶链式反应(real time PCR)检测Metrnl在结直肠癌组织及正常结肠组织中的转录水平。在细胞实验中,通过慢病毒介导短发夹RNA(shRNA)干扰技术敲减人结肠癌上皮细胞系Caco-2细胞中Metrnl表达,通过CCK8(Cell Counting Kit-8)细胞活力检测试剂盒、凋亡执行蛋白Caspase-3活力检测试剂盒、流式细胞检测Annexin V外翻等探究细胞在5-氟尿嘧啶(5-FU)作用下的存活和凋亡情况。结果 免疫组化检测显示Metrnl蛋白在人结直肠癌组织中增多,但real time PCR结果显示Metrnl mRNA水平降低(P<0.05)。敲减 Metrnl可抑制5-氟尿嘧啶诱导的细胞活力降低和细胞凋亡(P<0.05)。结论 由于肿瘤组织异构,分泌蛋白Metrnl在结直肠癌组织中蓄积,但Metrnl转录在结直肠癌中降低,Metrnl转录降低可能促进了结直肠癌的发生发展,提示该基因有望成为结直肠癌诊断和治疗的新靶点。     

小鼠Metrnl单克隆抗体的制备及鉴定

目的 制备抗小鼠Metrnl单克隆抗体,并进行初步筛选鉴定。方法 分别制备小鼠Metrnl多肽片段和全长蛋白作为免疫小鼠抗原,取免疫后小鼠脾细胞与SP2/0骨髓瘤细胞融合,筛选阳性杂交瘤细胞,并亚克隆获得稳定细胞株,制备腹水。用ELISA方法检测腹水抗体效价;用Western blot方法鉴定抗体。结果 由14种多肽抗原制备的56株单克隆抗体中,未筛选出可用于Western blot识别Metrnl的抗体;由全长蛋白制备的25株抗体中,有12株可识别Metrnl蛋白。结论 本实验成功制备了12株单抗,可用于识别检测小鼠Metrnl蛋白。     

肠上皮Metrnl基因敲除对肠道菌群以及溃疡性结肠炎的影响

目的 探讨肠上皮Metrnl对葡聚糖硫酸钠盐（DSS）诱导的溃疡性结肠炎小鼠模型的作用及其对肠道菌群调节机制的影响。方法 应用不同浓度的DSS（3%和1%）对C57 小鼠进行造模,确定实验条件。给予肠上皮Metrnl特异性敲除小鼠（Metrnl^(-/-)）及其对照小鼠（Metrnl^(+/+)）3%DSS造模5 d,观察模型小鼠的生存时间、体重、疾病评分（DAI）、结肠长度以及结肠组织切片病理学变化等指标。使用16S核糖体RNA基因测序技术检测肠道菌群组成。结果 与1%DSS相比,3% DSS可显著缩短C57小鼠的生存时间（P<0.05）,降低体重（P<0.05）,增加DAI评分（P<0.05）,缩短结肠长度（P<0.05）,增加病理学评分（P<0.05）。给予3%DSS造模5 d后,与对照组Metrnl^(+/+)小鼠相比,Metrnl^(-/-)小鼠体重下降更多（P<0.05）,DAI评分更高（P<0.05）,结肠长度更短（P<0.05）以及病理学评分更高（P<0.05）。检测16S核糖体RNA结果显示,Metrnl^(-/-)小鼠的肠道菌群多样性下降,拟杆菌（Bacteroidetes）和变形杆菌（Proteobacteria）显著降低,而厚壁菌（Firmicutes）显著升高。结论 Metrnl对3%DSS诱导的溃疡性结肠炎小鼠有保护作用,该作用可能与Metrnl对肠道菌群的调节作用相关。     

新型脂肪细胞因子Metrnl在糖脂代谢中作用的研究进展

新型脂肪细胞因子Meteorin-like(Metrnl)是神经营养调节因子Meteorin(Metrn)的同源蛋白。研究发现,Metrnl密切参与糖脂代谢性疾病,如血脂异常、肥胖、2型糖尿病、冠心病及非酒精性脂肪性肝病等的调控。其机制可能与诱导米色脂肪形成、调节腺苷酸活化蛋白激酶(AMPK)和过氧化物酶体增殖物激活受...     

Involvement of the secreted protein Metrnl in human diseases

Metrnl, a secreted protein expressed in white adipose tissue, has been identified as a novel adipokine. It is also highly expressed in barrier tissues, including the skin, intestinal and respiratory tract epithelium in both mice and humans. Research shows that its expression is upregulated by inflammation, chronic high-fat diets, exercise, cold exposure, etc., and it plays important roles in promoting neurite extension, enhancing white fat browning, improving insulin sensitivity, modulating lipid metabolism and regulating inflammatory response, the latter implying Metrnl is a new cytokine. These studies suggest that Metrnl could be a promising biomarker and a potential therapeutic target for the related diseases. For proving this, clinical studies need to be performed to bridge the gap between bench and bedside. In this paper, we summarize the progress in recent clinical research on Metrnl. Most of these clinical studies are designed to confirm the relationship between circulating Metrnl and metabolic or cardiovascular disease (type 2 diabetes and coronary heart disease), or immune inflammation-related diseases, such as colitis, psoriasis and arthritis. Although blood Metrnl seems to fluctuate and are affected by many factors, such as drugs, physical exercise, and cold exposure, these clinical studies provide reliable clues that Metrnl is associated with coronary heart disease, inflammation-related diseases, etc. Nevertheless, the roles of Metrnl in some diseases such as nervous system diseases remain unclear, and its putative involvement should be further clarified. These studies could promote the application of Metrnl in clinic as a new therapeutic target.     

Association of Meteorin-Like Hormone with insulin resistance and body composition in healthy Iranian adults

Background and aimsSedentary behavior and/or physical inactivity are modifiable risk factors for noncommunicable diseases. Myokines are one of the mediators of physical activity health benefits. Relationship between regular physical activity (RPA) and baseline plasma Meteorin-Like Hormone (Metrnl) has not been explored in human. Hence, we compared baseline plasma Metrnl between sedentary individuals and ones with recreational physical activities, and role of Metrnl as a biological messenger between physical activity and insulin resistance and body composition was also explored.MethodsForty healthy young men (aged: 21 ± 2.1 yrs; BMI: 23 ± 3.44 kg/m²) completed the study. Participants were equally assigned into two groups of control (sedentary) and case (recreational athletes). Baseline plasma Metrnl, glucose, insulin and body composition components and insulin resistance index (HOMA-IR) were assessed under resting conditions.ResultsExcept for baseline blood glucose, baseline plasma Metrnl, insulin, HOMA-IR and body mass index and body fat percentage were similar between two groups (P > 0.05). However, after Metrnl correction for the degree of insulin resistance index (Metrnl/HOMA-IR), recreational athletes showed a significantly greater baseline compared to sedentary subjects (P < 0.05). Baseline blood glucose showed a negative and significant correlation with baseline plasma Metrnl (P < 0.05).ConclusionsBaseline plasma Metrnl is correlated with regular physical activity and insulin sensitivity, but not with body composition parameters. Metrnl may be one possible mediator of the beneficial effects of PA on insulin sensitivity in healthy humans. Hence, increasing awareness of the benefits of physical activity and incorporating physical activity into lifestyle are of great importance for people with non-communicable diseases.     

Metrnl在肥胖小鼠模型中的表达

目的:探讨肥胖对小鼠各组织中Metrnl表达的影响。方法:高脂饮食4个月诱导小鼠肥胖,实时定量PCR与免疫组织化学法检测正常饮食与高脂饮食小鼠肝、骨骼肌、肾、结肠及脂肪组织中Metrnl mRNA与蛋白的表达。结果:高脂饮食增加了小鼠的体质量和白色脂肪量。同时,高脂饮食显著增加了白色脂肪组织Metrnl mRNA与蛋白的水平,但未增加肝、骨骼肌、肾、结肠组织中Metrnl的表达。结论:肥胖特异性增加脂肪组织中Metrnl的表达,从而形成"肥胖-脂肪组织上调Metrnl表达-代谢改善"的反馈调节通路。     

糖尿病视网膜病变患者血清Metrnl和鸢尾素水平变化及其临床意义

目的　探讨糖尿病视网膜病变（DR）患者血清Metrnl和鸢尾素（Irisin）水平变化及其临床意义,以期为DR患者的诊治提供新思路。方法　收集2020年3月至2021年9月就诊于济南市第八人民医院的2型糖尿病患者120例,根据是否合并视网膜病变和病变程度分为非DR组（NDR组,n=39）、非增生型DR组（NPDR组,n=43）、增生型DR组（PDR组,n=38）。同期选取健康体检者40人为正常对照组（NC组）。抽取各受试者的静脉血,分离血清,采用酶联免疫吸附试验检测其血清Metrnl和Irisin水平,并测量体重指数（BMI）、空腹血糖（FPG）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、超敏C反应蛋白（hs-CRP）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白1（MCP-1）、胰岛素抵抗指数（HOMA-IR）等指标。采用Spearman相关分析法分析患者血清Metrnl与Irisin水平、糖尿病病程、BMI、FPG、TG、TC、LDL-C、HDL-C、HbA1c、FINS、hs-CRP、IL-6、TNF-α、MCP-1、HOMA-IR的相关性。采用受试者工作特征（ROC）曲线分析血清Metrnl和Irisin水平对DR的诊断价值,采用多因素logistic回归分析DR发生的影响因素。结果　NDR组、NPDR组和PDR组患者血清Metrnl和Irisin水平均低于NC组（均为P<0.05）。NPDR组和PDR组患者血清Metrnl和Irisin水平均低于NDR组（均为P<0.05）,且PDR组患者血清Metrnl和Irisin水平降低更明显,NPDR组和PDR组患者血清Metrnl和Irisin水平比较差异均有统计学意义（均为P<0.05）。相关性分析显示,患者血清Metrnl水平与Irisin水平呈正相关（r=0.612,P<0.01）,但与DM病程（r=-0.473,P=0.000）、TG（r=-0.286,P=0.021）、HbA1c（r=-0.347,P=0.007）、HOMA-IR（r=-0.179,P=0.034）、TNF-α（r=-0.328,P=0.018）、IL-6（r=-0.196,P=0.030）和MCP-1（r=-0.272,P=0.025）均呈负相关。ROC分析结果显示,血清Metrnl和Irisin诊断DR的ROC曲线下面积分别为0.762和0.674,而两者联合诊断DR的ROC曲线下面积为0.858,灵敏度和特异度均高于血清Metrnl或血清Irisin单独诊断。logistic回归分析结果显示,糖尿病病程、HbA1c、MCP-1、血清Irisin和Metrnl水平均为DR发生的独立影响因素。结论　DR患者血清Metrnl和Irisin水平降低,且与患者病情程度相关,可能在糖脂代谢和炎症反应方面影响DR发生发展,对DR的诊断有一定预测价值。     

2型糖尿病患者血清Metrnl水平与骨密度的相关性研究

目的 探讨2型糖尿病(diabetes mellitus type 2,T2DM)患者血清Metrnl浓度与骨密度的相关性及其影响因素。方法 选取江苏大学附属医院就诊的T2DM患者146例,对所有受试者进行糖耐量、胰岛素兴奋实验、血生化检测等。ELISA检测血清Metrnl水平。所有受试者均接受双能X线骨密度仪检测,根据骨密度结果分为T2DM合并骨密度(bone mineral density, BMD)正常组和BMD异常组。结果 与T2DM合并BMD正常组相比,T2DM合并BMD异常组血清Metrnl水平显著升高(P<0.05)。进一步在调整性别、年龄等因素后,T2DM患者血清Metrnl水平与第1腰椎(L1)、L2、L3、L2～L4、L1～L4等BMD值,以及L1～L4 T值呈显著负相关(P<0.05)。Logistic回归结果显示,T2DM患者血清Metrnl水平与骨量异常独立相关。ROC曲线模型分析结果显示,血清Metrnl预测T2DM患者骨量异常的曲线下面积为0.720(95%CI=0.638～0.802,P<0.001)。结论T2DM合并BMD异常患者血清...