Explore Potential Markers Of Common TCM Syndromes In Congestive Heart Failure Based On CaN-NFAT3 Pathway

Objectives: Through explore dynamic changes of key proteins in CaN-NFAT3 pathway in various samples of Qi-deficiency-blood-stasis syndrome,Qi-yin-deficiency syndrome and Yang-deficiency-water-overflowing syndrome to clarify potential markers of CHF common Syndromes.Methods: From December 2018 to December 2020,30 patients in each group of CHF with Qi-deficiency-blood-stasis syndrome,Qi-yin-deficiency syndrome and Yang-deficiency-water-overflowing syndrome were collected from multicenter.Serum,urine and tongue coating fluid were collected at baseline,7 days and 14 days respectively.(1)The contents of CaN,NFAT3 and GATA4 in serum,urine and tongue coating fluid were determined by enzyme linked immunosorbent assay.(2)With spearman,Pearman correlation analysis,multiple correspondence analysis and other methods,comprehensively analyzed the correlation between the expression of CaN,NFAT3 and GATA4 and the clinical indexes such as cardiac function grade,B-type brain natriuretic peptide and left ventricular ejection fraction.(3)With receiver operating curve,established the diagnostic threshold of CaN,NFAT3 and GATA4 in CHF common Syndromes.Results: 30 patients in each group of CHF with Qi-deficiency-blood-stasis syndrome,Qi-yin-deficiency syndrome,Yang-deficiency-water-overflowing syndrome and western medicine control group were collected from multiple centers,and another 30 healthy controls were included.(1)The expression levels of CaN,NFAT3 and GATA4 in serum,urine and tongue coating fluid of CHF patients were higher than those of healthy people(P<0.01).Compared with the syndrome of Yang-deficiency-water-overflowing,the contents of various proteins in different periods,various samples of Qi-deficiency-blood-stasis syndrome and Qi-yin-deficiency syndrome were decreased(P<0.01).Compared with Qi-deficiency-blood-stasis syndrome,the content of GATA4 decreased in Qi-yin-deficiency syndrome on 7 days(P<0.05).The protein contents of CaN,NFAT3 and GATA4 in various samples of Qi-deficiency-blood-stasis syndrome,and Qi-yin-deficiency syndrome gradually decreased with the advance of treatment on the7 and 14 days,and there was no statistical difference compared with normal group(P>0.05).There was also a downward trend in the contents of various proteins in Yang-deficiency-water-overflowing syndrome,but it was still higher than that in normal group,and there was a statistical difference(P<0.05).(2)The expression levels of CaN,NFAT3 and GATA4 in serum,urine and tongue coating fluid were positively correlated with cardiac function grade and BNP,and increased gradually according to the order of Qi-deficiency-blood-stasis syndrome,Qi-yin-deficiency syndrome and Yang-deficiency-water-overflowing syndrome.The expression levels of CaN,NFAT3 and GATA4 in serum,urine and tongue coating fluid were negatively correlated with LVEF and decreased gradually with this order.(3)CaN and GATA4 in serum,NFAT3 in urine,CaN in tongue coating fluid at baseline and CaN in tongue coating fluid on 7days had higher diagnostic value for Qi-deficiency-blood-stasis syndrome,the threshold values were respectively,at baseline serum CaN:878.10 pg/ml,serum GATA4:3777.49 pg/ml,urine NFAT3:415.18 pg/ml,tongue coating fluid CaN:557.84pg/ml;7 days tongue coating fluid CaN:474.81 pg/ml.CaN in the tongue coating fluid at baseline had higher diagnostic value for Qi-yin-deficiency syndrome,the threshold value was 592.08 pg/ml.CaN and GATA4 in serum,CaN,NFAT3 and GATA4 in urine,CaN and NFAT3 in tongue coating fluid at baseline,CaN in serum and tongue coating fluid on 7 days,CaN in tongue coating fluid on 14 days for Yang-deficiency-water-overflowing syndrome had higher diagnostic value,the threshold values were respectively,at baseline serum CaN:1080.36 pg/ml,serum GATA4:3923.60 pg/ml,urine CaN:832.05 pg/ml,urine NFAT3:428.50 pg/ml,urine GATA4:3076.29 pg/ml,tongue coating fluid CaN:638.03 pg/ml,tongue coating fluid NFAT3:412.48 pg/ml;7 days serum CaN:933.82 pg/ml,tongue coating fluid CaN:598.14 pg/ml;14 days tongue coating fluid CaN:587.52 pg/ml.Conclusions:(1)The expression levels of CaN,NFAT3 and GATA4 in serum,urine and tongue coating fluid of CHF patients were higher than those of healthy people.Compared with the syndrome of Yang-deficiency-water-overflowing,the contents of CaN,NFAT3 and GATA4 of Qi-deficiency-blood-stasis syndrome and Qi-yin-deficiency syndrome were decreased.The dynamic change trend of protein expression in CHF common TCM syndromes was consistent in different periods.The protein expressions of CaN,NFAT3 and GATA4 in serum,tongue coating fluid and urine samples with the same syndrome of CHF showed synchronous and different changes.(2)CaN,NFAT3 and GATA4 proteins in serum,urine and tongue coating fluid of CHF patients were closely correlated with BNP and other clinical indexes,the protein expression level and the change of its content in different periods can directly reflect the different TCM syndromes of CHF,which can be used as the internal basis to identify the common TCM syndromes of CHF.(3)The key proteins of the CaN-NFAT3 pathway in the samples have good diagnostic value for common TCM syndromes of CHF.Compared with different proteins in serum and urine samples.CaN in tongue coating fluid samples has higher diagnostic value for CHF common syndromes and different thresholds of severity of CHF.