| Cardiorenal Syndrome(CRS)is a clinical syndrome characterized by interaction of heart and kidney bi-dysfunction,ultimately resulting into accelerated failure of the two organs.Current CRS clinical treatment can not completely reverse the cardiac and renal interactions and improve its prognosis,thus this has become a global interdisciplinary clinical problem.At present,it is very important to further explore CRS pathogenesis and its effective targets and propose new and effective treatment methods.The purpose of this study was to investigate the effect of Zhenwu Decoction(ZW-D)on cardiorenal function in CRS and its mechanism,using high performance liquid chromatography(HPLC)to assess its quality control and component analysisMethods:1.A single-center randomized controlled trial was conducted among 100 patients with CRS who were randomly assigned to Zhenwu decoction group(n=50)and control group(n=50).The control group was treated with routine clinical therapy,while Zhenwu decoction group was treated with ZW-D on the basis of routine clinical therapy.All patients routine examinations were carried out in Zhujiang Hospital.ELISA kit was used to detect IL-1β,IL-18 and indoxyl sulfate(IS).2.50 SD rats were randomly divided into 5 groups:sham group,MI(myocardial infarction)+STNx(5/6 nephrectomy)group,MI+STNx+ZW-D-low dose group,MI+STNx+ZW-D-medium dose group and MI+STNx+ZW-D-high dose group.Creatinine,urea nitrogen,24 hour urine protein were detected using a kit test.BNP,IL-1β,IL-18 and IS were assessed by ELISA kit.Cardiac function was assessed using echocardiography,heart and kidney pathological changes were observed through HE staining,collagen deposition in cardiorenal tissues was detected by Masson staining,and pro-fibrotic proteins related to cardiorenal fibrosis were evaluated via immunofluorescence and at the same time,Western Blot was used to detect the related pathway proteins.3.Using HPLC to analyze the composition of ZW-D,including nine kinds of Chinese medicine monomer reference substances,such as paeoniflorin and albiflorin,the HPLC fingerprint of ZWD granules,and the linear relationship between the characteristic peak area and concentration of each component were established,and the quantitative detection of each component in ZW-D was carried out.Results:1.There was no statistical difference between the control and ZW-D groups before enrollment,comparing the difference between the two groups before and after treatment,it was found that serum NT-poBNP,IL-1β,IL-18 levels in the ZW-D group were significantly lower than that in the control group,eGFR level was reduced in the control group but increased in the ZW-D group,serum IS was elevated in the control group while decreased in the ZW-D group.2.ZW-D improved the cardiac function in CRS rats,the middle dose group significantly reduced BNP levels,and echochardiography showed that ZW-D improved cardiac contractile function and ventricular remodeling.ZW-D improved renal function by lowering Scr,BUN levels.In the middle dose groups ZW-D reduced serum IS levels,and IL-1β,IL-18 levels were significantly reduced in middle and high dose groups.The fibrosis of cardiorenal tissues was improved as shown through HE and Masson staining,especially in the middle dose group.The results of immunofluorescence and Western Blot showed that ZW-D decreased the expression of pro-fibrotic proteins which include collagen Ⅰ,TGF-β andα-SMA,especially in the middle dose group.Through Western Blot,it was found that ZW-D could significantly down-regulate the ASK1/MAPK/NF-κB and ASK1/NLRP3/caspas-1/IL-1β pathways and display a protective role.3.The ZW-D fingerprint was established by HPLC technology,and the presence of 9 reference substances in ZW-D was successfully detected.Paeoniflorin was the highest content,followed by albiflorin and gallic acid,and the remaining components were less.Conclusion:ZW-D can improve the cardiorenal functions and fibrosis in CRS,which may play a protective role through ASK1/MAPK/NF-κB and ASK1/NLRP3/caspas-1/IL-1β pathways.The anti-inflammatory and improving cardiorenal function effects of 9 components contained in ZW-D such as paeoniflorin and albiflorin may provide a material basis for the therapeutic effect of ZW-D in CRS... |
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