Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat co...Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.展开更多
文摘目的探讨妊娠糖尿病(gestational diabetes mellitus,GDM)患者血清、脐血及胎盘组织中的内脏脂肪组织(Visfatin)、脂肪因子趋化素(Chemerin)的表达变化及与患者发生胰岛素抵抗的关系。方法选取阜阳市人民医院2018年12月~2020年4月妊娠分娩的GDM孕妇100例作为GDM组、糖耐量正常孕妇100例作为NGT组。统计分析两组的一般资料、血糖指标、血脂指标,检测两组研究对象血清、脐血、胎盘组织中的Visfatin,Chemerin表达水平,分析Visfatin,Chemerin表达与胰岛素抵抗指数(HOMA-IR)的相关性;通过重组慢病毒载体构建Visfatin,Chemerin过表达的3T3-L1脂肪细胞,分析Visfatin,Chemerin过表达对3T3-L1脂肪细胞增殖、葡萄糖消耗量、Akt及pAkt蛋白表达的影响。结果GDM组的FPG(5.84±0.52mmol/L),Fins(18.96±3.75μU/ml),HbA1c(6.42%±0.89%),HOMA-IR(2.48±0.66),TC(5.22±0.57mmol/L)和TG(2.41±0.43mmol/L)测定值均高于NGT组(4.61±0.40mmol/L,12.53±2.20μU/ml,5.31%±0.70%,1.51±0.42,4.86±0.49mmol/L和2.18±0.34mmol/L),差异具有统计学意义(t=18.749,14.789,9.803,12.399,4.789,4.196,均P<0.05);GDM组和NGT组的HDL-C(1.64±0.22mmol/L vs 1.70±0.24mmol/L),LDL-C(3.23±0.67 mmol/L vs 3.10±0.54 mmol/L)和ALB(37.84±3.02g/L vs 38.44±3.30 g/L)测定值比较,差异均无统计学意义(t=-1.843,1.511,-1.341,均P>0.05);GDM组的血清、脐血、胎盘组织中的Visfatin(10.55±2.41pg/ml,9.87±2.26 pg/ml,0.421±0.093/βactin)和Chemerin(233.0±47.6 ng/ml,438.1±95.0 ng/ml,1.338±0.207/βactin)测定值均高于NGT组(6.39±1.05pg/ml,6.11±0.94pg/ml,0.235±0.074/βactin;155.7±30.6ng/ml,218.7±76.8ng/ml,0.905±0.152/βactin),差异具有统计学意义(t=13.660~17.960,均P<0.05);GDM组的血清、脐血和胎盘组织中的Visfatin和Chemerin水平与HOMA-IR测定值均呈显著的正相关关系(r=0.357~0.583,均P<0.05);在细胞实验中,Chemerin过表达组与Visfatin过表达组的3T3-L1脂肪细胞葡萄糖消耗量均低于Chemerin空载组、Visfatin空载组(t=-12.175,5.319,均P<0.05);Chemerin过表达组和Visfatin过表达组的3T3-L1脂肪细胞增值A值高于Chemerin空载组与Visfatin空载组(t=-13.765,6.034,均P<0.05);Chemerin过表达组和Visfatin过表达组Akt与pAkt蛋白相对表达强度低于Chemerin空载组和Visfatin空载组(t=-15.938~-10.352,均P<0.05)。结论GDM患者血清、脐血和胎盘组织中的Visfatin和Chemerin表达水平显著升高,并且与胰岛素抵抗有正相关性,其作用机制可能与下调Akt和pAkt蛋白表达有关。
基金Supported by The Swiss National Science Foundation, No. 32003B-134963/1"Sir Jules Thorn Trust Reg" Foundation+4 种基金Gustave and Simone Prévot Foundation to Montecucco FEU FP7 AtheroRemo, No. 201668Swiss National Science Foundation, No. 310030B-133127Novartis FoundationSwiss Heart Foundation to Mach F
文摘Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD.
