Objective To review the current knowledge about the pathophysiological mechanisms,preclinical models,novel contributors and potential therapies of cardiorenal syndrome.Data sources The literature concerning cardioranal syndrome in this review was collected from PubMed published in English up to January 2014.Study selection Original articles and critical reviews related to cardiorenal syndrome were selected and carefully analyzed.Results Cardiorenal syndrome is a condition characterized by kidney and heart failure where failure of one organ worsens the function of the other thus further accelerating the progressive failure of both organs.The pathophysiology of cardiorenal syndrome is not fully understood,but may be caused by a complex combination of neurohormonal system activation,endothelial dysfunction,proteinuria,oxidative stress,uremic toxins and other factors.Managing cardiorenal syndrome is still a major therapeutic challenge in clinical practice because many of the drugs used to control heart failure can worsen renal function,and vice versa.Non-dialyzable uremic toxins,such as indoxyl sulfate,causing detrimental effects on the heart and kidney as well as stimulation of inflammatory responses,may be an effective therapeutic target for cardiorenal syndrome.Conclusions Suitable disease models of cardiorenal syndrome are urgently needed to investigate the pathophysiology and effective therapeutic approaches to the condition.Non-dialyzable protein-bound uremic toxins that may have cardiac and renal effects may provide therapeutic benefit to cardiorenal syndrome patients.
Fu QiangCao LongxingLi HuangWang BinghuiLi Zhiliang
目的观察尿毒症毒素硫酸吲哚酚(IS)是否促进巨噬泡沫细胞脂滴的蓄积,以及对细胞内B类1型清道夫受体(SR-B1)表达和核因子NF-κB活化的影响。方法体外佛波酯(PMA)诱导人源单核细胞系THP-1分化为巨噬细胞,加入氧化低密度脂蛋白(ox-LDL)培养促进巨噬细胞泡沫化,随后以不同浓度的IS干预巨噬泡沫细胞,油红O染色观察细胞内脂滴变化,实时PCR和Western blotting检测SR-B1 m RNA和蛋白表达的水平,ELISA法检测NF-κB活化情况;经NF-κB抑制剂四氢化吡咯二硫代氨基甲酸酯(PDTC)预处理后IS再干预,实时PCR检测巨噬泡沫细胞内SR-B1 m RNA表达的变化。结果与对照组(IS 0μmol/L)比较,IS干预后巨噬泡沫细胞内脂滴明显增加,随着IS浓度的升高,细胞内脂滴逐渐增加;IS干预后巨噬泡沫细胞的NF-κB活化程度增高,差异有统计学意义(P<0.05)。与对照组比较,细胞在不同浓度的IS(2.5、25、250μmol/L)处理下,SR-B1 m RNA和蛋白的表达下降,随着IS浓度的增加,SR-B1和蛋白逐渐减少,呈现浓度依赖性,差异有统计学意义(P<0.05)。PDTC预处理后SR-B1m RNA表达增加,差异有统计学意义(P<0.05)。结论 IS抑制SR-B1 m RNA和蛋白的表达,增加THP-1源性巨噬泡沫细胞胆固醇的蓄积,促进巨噬细胞泡沫化,从而促进动脉粥样硬化。NF-κB活化可能是IS抑制SR-B1 m RNA表达的可能机制之一。
