Characterization of the human chemerin receptor--ChemR23/CMKLR1--as co-receptor for human and simian immunodeficiency virus infection, and identification of virus-binding receptor domains

Studies were conducted to elucidate co-receptor spectrum and function of the inflammatory receptor, CMKLR1/ChemR23, which was recently identified as the receptor for the cystatin-like chemoattractant, TIG2, also named chemerin. An infection model was applied based on stably transfected NP-2.CD4 host cells expressing various co-receptor constructs and exposed to panels of HIV-1, HIV-2 and SIV primary isolates. In a panel of 27 HIV-1 isolates tested, 12 isolates could use CMKLR1/ChemR23. As expected from a relatively high sequence homology with the extracellular domains of CCR3, HIV-1 isolates showing R3 tropism were particularly efficient in using CMKLR1/ChemR23. In addition, 5 out of 7 HIV-2 isolates and 13 out of 15 SIV (SMM-3 origin) used CMKLR1/ChemR23, in accordance with the previously documented ability of these isolates to use several co-receptors. In order to define important extracellular epitopes for the viral interaction, a hybrid receptor model was applied. This was based on the fact that the rat receptor, although structurally very similar to the human orthologue, was inefficient as viral co-receptor. When the rat receptor was "humanized" to include regions unique to the human receptor (N-terminus or second extracellular loop), exposure to HIV-1, HIV-2 and SIV isolates resulted in infection. The relative importance of the two critical receptor regions differed between HIV-1/HIV-2 on the one hand and SIV on the other. The results strongly support that the chemerin receptor, in the presence of CD4, functions as a "minor co-receptor" promoting infection by these classes of viruses.     

Chemerin与动脉粥样硬化的关系

新发现的脂肪细胞因子chemerin不仅是传统意义上的趋化蛋白,还通过多种途径参与动脉粥样硬化的发展.其可能机制是参与胰岛素抵抗,糖、脂代谢异常及代谢综合征的发生,进而促进动脉粥样硬化的发展;直接影响血管内皮细胞的炎性反应状态,促进单核巨噬细胞黏附、迁移以及泡沫细胞的形成;促进新生血管形成,使斑块不稳定性增加,参与斑块破裂、血栓形成.深入研究chemerin与动脉粥样硬化的关系将为动脉粥样硬化的防治提供新靶点.     

血浆趋化素与糖尿病肾病的相关性

目的 观察不同阶段糖尿病肾病患者血浆趋化素（chemerin）水平的变化,探讨其与糖尿病肾病的相关性。方法 健康对照组为65名健康体检者,2型糖尿病患者195例（2型糖尿病组）分为正常白蛋白尿组、微量白蛋白尿组及临床白蛋白尿组,每组各65例。用酶联免疫法检测4组研究对象的血浆趋化素浓度。结果 2型糖尿病组血浆趋化素浓度为(150.20±21.99)μg/L, 明显高于健康对照组［（62.13±18.90）μg/L］（P＜0.001）;微量白蛋白尿组［(143.63±22.33) μg/L］ 及临床白蛋白尿组［(173.21±23.91) μg/L］血浆趋化素浓度高于正常白蛋白尿组［(100.35±20.11) μg/L］（P均＜0.01）;临床白蛋白尿组又高于微量白蛋白尿组(P＜0.01);多元回归分析显示2型糖尿病伴肾病患者趋化素水平与糖化血红蛋白(β=0.216,P=0.038)、总胆固醇(β=1.867,P=0.048)、高敏C反应蛋白(β=12.330,P＜0.001)、尿白蛋白(β=37.184,P＜0.001)均独立相关。结论 2型糖尿病患者血浆趋化素水平升高,可作为早期糖尿病肾病的检测指标之一。     

Serum chemerin level in women with PCOS and its relation with the risk of spontaneous abortion

Background and aim: Insulin resistance (IR) was recognized as a risk factor for the occurrence of abortion in patients with polycystic ovary syndrome (PCOS). Chemerin was an adipokine which could induce IR and associated with reproductive process closely. However, few studies have inquired the relativity between chemerin and the occurrence of abortion in patients with PCOS. The aim of this study was to evaluate the relationship between serum chemerin and the occurrence of abortion in women with PCOS.

Methods: We recruited 198 women with PCOS to participate in our study. On the third day of menstrual cycle or a random day in women with amenorrhea, we obtained their venous blood and measured the fasting insulin, fasting plasma glucose, total cholesterol, high density lipoprotein cholesterol, triglyceride, chemerin, and hormones including FSH, E2, P, PRL, LH, and T. Additionally, BMI, HOMA-IR and LH/FSH of each subject were calculated. Finally, 58 of them were included in the study, in which 30 of them had normal pregnancy and the other 28 had an early miscarriage. We compared the biochemical characteristics between the normal pregnancy group and abortion group by independent-samples t test.

Results: In our study, those with a normal pregnancy had a lower level of BMI, FINs, HOMA-IR, and chemerin compared to abortion patients (p?p?Conclusions: Serum chemerin level is associated with the occurrence of abortion in patients with PCOS. Thus, serum chemerin may serve as a biomarker to identify pregnant women with PCOS who are at particular risk for later abortion, and who may benefit from prevention strategies.     

维生素D制剂干预对单纯性肥胖学龄前儿童免疫功能及血清脂肪因子水平的影响

目的探讨维生素D制剂干预对单纯性肥胖学龄前儿童血清免疫球蛋白、T淋巴细胞亚群及脂肪因子(网膜素-1、趋化素、内脂素)水平的影响。方法选取2018年2月至2019年2月诊治的单纯性肥胖学龄前儿童80例作为研究对象,均在饮食及运动干预基础上于每日早餐后口服维生素D制剂,连续服用6个月。观察干预前后体重指数(BMI)及BMI标准差积分(BMISDS),使用化学发光法检测血清25-羟维生素D3[25-(OH)D3]、网膜素-1、趋化素及内脂素水平,使用免疫散射比浊法检测血清免疫球蛋白(Ig)A、IgG、IgM水平,使用流式细胞仪检测血清T淋巴细胞亚群CD3^+、CD4^+、CD8^+绝对计数,用MRFlow分析软件计算CD4^+/CD8^+。结果干预后单纯性肥胖学龄前儿童,其BMI、BMISDS显著低于干预前,血清25-(OH)D3水平明显高于干预前(P<0.01);血清IgA、IgG水平显著高于干预前,IgM水平明显低于干预前(P<0.01);CD3^+、CD4^+水平及CD4^+/CD8^+显著高于干预前,CD8^+水平明显低于干预前(P<0.01);血清网膜素-1水平显著高于干预前,趋化素、内脂素水平明显低于干预前(P<0.01)。单纯性肥胖学龄前儿童BMI、BMISDS与血清IgM、CD8^+、趋化素及内脂素水平分别呈正相关关系,与血清IgA、IgG、CD3^+、CD4^+、CD4^+/CD8^+、网膜素-1水平分别呈负相关关系(P<0.05,P<0.01);血清25-(OH)D3水平与血清IgA、IgG、CD3^+、CD4^+、CD4^+/CD8^+、网膜素-1水平分别呈正相关关系,与血清IgM、CD8^+、趋化素及内脂素水平分别呈负相关关系(P<0.05 P<0.01)。结论适量补充维生素D可明显改善单纯性肥胖学龄前儿童免疫功能,提高血清网膜素-1水平,降低血清趋化素、内脂素水平。     

依那普利叶酸片联合雌二醇片/雌二醇地屈孕酮片治疗围绝经期H型高血压的疗效观察

目的分析围绝经期H型高血压中依那普利叶酸片联合雌二醇片/雌二醇地屈孕酮片的应用效果。方法随机选取平湖市第一人民医院2017年6月-2019年3月诊治的120例围绝经期H型高血压患者,采取随机数字表法分为两组,每组60例。对照组单纯采取依那普利叶酸片治疗,观察组在此基础上采用雌二醇片/雌二醇地屈孕酮片治疗。结果治疗3月后观察组Kupperman评分明显优于对照组,两组比较差异有统计学意义(P<0. 05),但两组血压控制效果经检验,差异无统计学意义(P>0. 05)。治疗后观察组Chemerin蛋白、生长分化因子-15 (GDF-15)及同型半胱氨酸(Hcy)水平显著低于对照组,差异有统计学意义(P<0. 05)。结论应用依那普利叶酸片联合雌二醇片/雌二醇地屈孕酮片治疗围绝经期H型高血压可有效改善血压控制效果,同时还可改善血脂代谢及胰岛素抵抗,值得临床推广。     

Chemerin在代谢综合征相关肿瘤治疗中的作用及机制

代谢综合征是一组以胰岛素抵抗为核心，多种代谢异常簇集发生在同一个体的临床状态，与许多恶性肿瘤的发生有关。脂肪组织可分泌大量脂肪因子，参与代谢综合征及其相关肿瘤的发生发展。Chemerin是近年新确认的脂肪因子，具有促进脂肪分化和炎症反应、影响胰岛素抵抗及调节脂代谢等作用，参与代谢综合征极其相关疾病的进程。此外，作为一种趋化因子，Chemerin可介导肿瘤微环境中多种免疫细胞募集，发挥抗肿瘤作用。本文将针对Chemerin在代谢综合征相关肿瘤治疗中的作用及机制进行综述。     

OSAS患者血浆chemerin的临床研究

目的比较肥胖组、轻中重度OSAS患者组之间血浆chemerin水平,分析血浆chemerin水平的相关因素。方法用酶免法检测24例单纯肥胖者和20例轻度、12例中度、28例重度OSAS患者血浆中的chemerin,并检查试验组的体块指数（BMI）、腰围、臀围、腰臀比（WHR）、血压,PSG检测最低氧饱和度、低通气指数等指标。结果肥胖组和OSAS组之间血浆chemerin水平比较差异无统计学意义,不同程度OSAS之间血浆chemerin水平比较差异也无统计学意义。血浆chemerin和WHR有关,呈正相关（R=0.268,P〈0.05）,chemerin和SBP有正相关关系（R=0.284,P〈0.05）,多因素回归分析显示,chemerin为因变量,收缩压和腰臀比进入方程（P〈0.05）。结论血浆chemerin水平与肥胖、血压具有相关性,与OSAS严重程度无明显相关,揭示chemerin可能在肥胖和相关心血管病的病理生理机制中发挥作用。     

普伐他汀对冠心病患者血脂、血浆 Chemerin 水平、超敏C 反应蛋白、血清脂联素的影响

目的 探讨普伐他汀对冠心病患者血脂、血浆脂肪因子趋化素（Chemerin）水平、超敏C反应蛋白（hs—CRP）、血清脂联素的影响。方法 收集2010年1月～2013年12月湖北省荣军医院老年病科收治的118例冠心病患者,并将其随机分为常规治疗组和普伐他汀组,观察治疗前后血浆Chemerin水平、hs—CRP、血清脂联素的变化,分析Chemerin、脂联素、hs—CRP与血脂浓度之间的相关性。结果 疗程结束后,普伐他汀组血浆Chemerin、hs—CRP、总胆固醇（TC）、三酰甘油（TG）及低密度脂蛋白胆固醇（LDL—C）水平均较常规治疗组显著降低（P〈0．01）,血清脂联素及高密度脂蛋白胆固醇（HDL—C）水平均较常规治疗组显著升高（P〈0．01）。血浆Chemerin与TG呈正相关（r=0．48,P〈0．01）;hs—CRP与HDL—C呈负相关（r=-0．21,P〈0．01）;血清脂联素与HDL—C呈正相关（r=0．56,P〈0．01）,与Chemerin、hs—CRP均呈负相关（r=-0．43、-0．36。P〈0．01）。结论 普伐他汀可以显著降低冠心病患者血脂水平,而且能提高血清脂联素水平以降低hs—CRP浓度及血浆Chemerin水平。     

脂肪因子chemerin研究进展

2007年,chemerin被确认为新脂肪因子。最新研究发现,chemerin及其受体chemerin re-ceptor(chemerinR)的基因在白色脂肪组织高表达,chemerin是调节脂肪细胞分化和代谢的一个新脂肪因子,也是与肥胖和代谢综合征组成部分相关的一个新脂肪因子。对于chemerin的深入研究,有望为治疗肥胖及其相关性疾病提供新途径。