Determination The Concentration Of Plasma IL-27 In Patients With Typye2 Cardiorenal Syndrome And Its Clinical Significance

Cardiorenal syndrome is the clinical syndrome that heart and renal damage.CRS is refers to the heart or kidney one organ of acute or chronic damage lead to the alteration of the second.Ronco in 2008, according to the organs(heart or kidney) onse by chronic or acute and successively, cardiorenal syndrome(CRS) can be divided into 5 types, including type Ⅱ CRS namely narrow cardiorenal syndrome, it refers to chronic heart failure lead to chronic renal insufficiency, its high incidence, 63% of patients with chronic heart failure can lead to chronic renal dysfunction. In the Acute Decompensated Heart Failure National Registry(ADHERE) of 105000 hospitalized patients with acute heart failure were investigated, 30% have a history of renal insufficiency, 21% of the patients serum creatinine > 2 mg/dl, 9% of the patients serum creatinine levels at 3 mg/dl; in another study of 754 outpatients with Heart failure, only 17% of patients creatinine clearance > 90 m L/min, 39% of the New York Heart Association(NYHA) class IV symptoms and 31% of patients with NYHA class III symptoms had a creatinine clearance < 30 m L/min. The mortality of cardiovascular disease is 10-20 times in chronic kidney disease(CKD), cardiovascular disease accounted for 50% of all deaths for patients with CKD. The above clinical data show that between the acute or chronic heart failure and renal insufficiency have a interaction which is a key to the pathogenesis of CRS. Early research suggests the pathogenesis of CRS is mainly through the following mechanisms: in the early of CHF in order to ensure the normal cardiac output, the sympathetic nervous system(SNS) and renin-angiotensin-aldosterone system(RAAS) enhanced excitability, leading to the increasing of plasma rennin 、 angiotensin Ⅱand aldosterone.Sustaining neurohormonal activation can lead to cardiac muscle cell necrosis and apoptosis,myocardial fibrosis, consequentlycausing ventricular remodeling, resulting in a decline in cardiac systolic function.Besides,plasma renin and angiotensin can cause efferent artery contraction and renal tubule capillaries osmotic pressure increases, the decline in glomerular filtration rate, as well as aldosterone can lead to the increased renal tubule fibrosis, finally the CHF patients with renal function injury. Due to there is no widely accepted clinical treatment guidelines about CRS, CRS treatment is still confined to the heart, kidney failure/function or only the pathogenesis of CRS targeted therapy. In view of the above the pathogenesis of CRS, including diuretics, beta-blockers, angiotensin converting enzyme inhibitors(ACEI) or angiotensin receptor blockers(ARB) and Erythropoietin(EPO) and continuous renal replacement therapy(CRRT), and other drugs had been applied in the treatment of CRS. Including ACEI and ARB drugs has become the cornerstone of treatment of CHF with CKD, these drugs can not only antagonism neurohormonal activation, improve myocardial remodeling, but also can reduce urine protein, to a certain extent, can delay the progression of the CHF and the deterioration of renal function, improvement of prognosis of patients with CHF and CKD. But there is no large-scale clinical trials show that these drugs can significantly improve the prognosis of CRS, especially the patients of type Ⅱ CRS mortality remains high, with poor prognosis. Prompting there have not been discovered other important mechanisms to promote the development of type Ⅱ CRS. Now research suggests the pathophysiology of type ⅡCRS may be related to the Neurohormonal activation, immune system, inflammation and the imbalance of NO and ROS. Inflammatory reaction with enhanced oxidative stress play an important role in the development of type CRS. Ⅱ Research have shown that the peripheral blood of type Ⅱ CRS patients proinflammatory factor, Interleukin-6(IL-6), tumor necrosis factor-a(TNF-a) increased significantly, and these proinflammatory factor expression increasing with deterioration of renal function and the decreasing restraining inflammation factor such as Interleukin-10(IL-10) and growth factor beta-β(TGF-β).Showing the imbalance of proinflammatory and anti-inflammatory is closely related to type Ⅱ CRS.Interleukins(IL-27)belong to IL6/ IL-12 the newest member of the family of cytokines, it have anti-inflammatory and proinflammatory two-way adjustment. IL-27 main through signal transducers activators transcription1(STAT1) and STAT3 two signaling pathways play biologic role. IL-27 activate STAT1 signaling pathways, inducing the expression of T- bet that helper T cells(TH1) cell specific transcription factor, promoting TH1 cells to produce interferon- γ(IFN-γ), and inhibition of regulatory T cells(Treg) secrete anti-inflammatory TGF-β; besides activating STAT1 and STAT3 signaling pathway inhibition of TH17 cells produce IL-17, promoting the type 1 regulatory T cells(Tr1) cell secretion of IL- 10 limit inflammation. IL- 27 had dual regulation effect to the differentiation of TH1 cells. Early in the inflammatory response, IL-27 main through TH1 cells play a role of proinflammatory differentiation, and in the late inflammatory response, IL-27 can be negative feedback regulation of TH1 cells, limiteing a strong inflammatory reaction, in order to maintain the immune balance.At present, the research has reported IL-27 associated with the progression of CHF, coronary heart disease. Animal experiments confirmed that IL-27 has the inhibitory effect of artery atherosclerosis. So IL-27 in type Ⅱ CRS needs further research. This experiment by observing the expression of IL- 27 in type Ⅱ CRS, analysis IL-27 relevance with type CRS from the Angle of clinical.ⅡObjective:To observe the concentration changes of IL-27 in type Ⅱcardiorenal syndrome, to explore the relation between IL-27 and type ⅡCRS.Materials and Methods 1.Clinical data Choose 120 patients with CHF admitted in our hospital,from November 2013 to August 2014, record the their gender, age, height, weight, blood pressure, NYHA class, risk factors, Hb, FBG, etiology, drug, the left ventricular ejection fraction, E/A value and other indicators. Choose 30 healthy people as control group. 2.Exclusion standard : acute and chronic infections, autoimmune diseases,activity rheumatism in 3 months,thyroid function is unusual, malignant tumor patients, clear liver and kidney function dysfunction. 3.Method : CHF patients according to glomerular filtration rate(GFR) < 60 ml/min,divided into type Ⅱ CRS group 70 cases and pure heart failure group of 50 cases, including type Ⅱ CRS group according to the New York heart association(NYHA)class, divided into gradeⅡ group 28 cases, gradeⅢ group 24 cases, grade Ⅳ group 18 cases; typeⅡ CRS group by glomerular filtration rate(GFR), divided into CKD3(GFR 30-59 ml/min)22cases, CKD4(GFR15-29 ml/min)25cases, CKD5(GFR < 15 ml/min) in 23 cases. 30 healthy people as control group was selected at the same period. Type CRS group, pure heart failure group and controⅡ l group was detected respectively in plasma IL-27(enzyme-linked immunosorbent method), BNP(direct chemiluminescence method), Cystain-c(Cys-c)(immune transmission turbidimetric assay, homocysteine(Hcy)(enzymatic cycling assay) and hs-CRP(immune turbidimetry) level changes. Heart function was measured by ultrasound cardiography.To observe different groups, type Ⅱcardiorenal different cardiac function classification and renal function stage serum IL-27, Cys-c, Hcy, BNP, LVEF, hs-CRP level changes. Analysis relevance of the IL- 27 withhypersensitive c-reactive protein(hs-CRP), B-type natriuretic peptide(BNP), Cystatin-c(Cys-c), Homocysteine(Hcy) and left ventricular ejection fraction(LVEF). 4、The statistical methods All data was analysis with SPSS18.0 software,Measurement data is expressed( mean± SD).adopting single factor variance analysis(One- way ANOVA) were compared among multiple groups, multiple comparison between groups using LSD method, if the heteroscedasticity is using Welch inspection, multiple comparison between groups using Dunnett’s T3 test, Correlation analysis of data was carried out by Pearson’s correlation analysis. A P value less than 0.05(P<0.05) was considered to indicate statistical significance.Result 1、Basic clinical data are analysised the comparison of Type Ⅱ CRS、 CHF group and healthy control group in age, sex, smoking, body mass index, blood lipid, there was no statistically significant difference(P> 0.05); the FBG in Type Ⅱ CRS and pure heart failure group was higher than those of healthy controls(P< 0.05),FBG was no statistically significant difference between Type Ⅱ CRS and CHF group(P> 0.05); the Hb in Type Ⅱ CRS and pure heart failure group was lower than those of healthy controls(P< 0.05), and type Ⅱ CRS group was lower thanthose of pure heart failure group(P< 0.05); 2 、 IL-27 and other indicators levels were analysised in Type Ⅱ CRS,CHF group and healthy control group There were significant difference of IL-27、BNP、hs- CRP、Hcy、Cys-c 、LVEF levels in each group(P< 0.05), and IL-27、BNP、hs-CRP、Hcy、Cys-c levels were higher in type Ⅱ CRS,CHF than control group(P< 0.05); the LVEF in Type Ⅱ CRS, CHF was lower than those of healthy controls(P< 0.05), and type Ⅱ CRS group is lower than CHF group(P< 0.05). 3. IL-27 and other indicators levels were analysised in Type Ⅱ CRS group according to the NYHA classification IL-27, Hcy, Cys-c, hs-CRP, BNP levels rising with the rising of cardiac function grading(P< 0.05), and LVEF and decreased with the increase of cardiac function grading(P< 0.05); Cysc level in grade Ⅳ was higher than gradeⅡ、 grade Ⅲ(P < 0.05); Cysc level was no statistically significant difference between gradeⅡand grade Ⅲ(P > 0.05). 4. IL-27 and other indicators levels were analysised in Type Ⅱ CRS group according to CKD stage IL-27, Hcy, Cys-c, hs-CRP, BNP levels rising with the rising of CKD stage(P< 0.05), and LVEF in different stages of chronic kidney disease(CKD), there was no statistically significant difference(P> 0.05).5. By Pearson, linear correlation analysis IL-27 and observation index IL – 27 with hs-CRP, the BNP, Hcy, Cys-c level were positively correlated(P < 0.05), and negatively correlated with LVEF(P< 0.05). 6. Multiple linear regression analysis showed that the hs- CRP, BNP, Hcy, Cys –c were independent influence factors of IL – 27.Conclusion IL-27 increased expression in the type Ⅱ CRS patients, and IL-27 were positively correlated with Hcy、 Cys-c、hs-CRP、 BNP levels, negative correlation with LVEF, and IL-27 levels increase with the deterioration cardiac function and renal function, prompt IL- 27 is closely related to development of type II CRS.