| Cirrhosis cardiomyopathy(CCM)is a subclinical change in the intrinsic condition of the heart in cirrhotic patients without significant abnormalities in the structure and function of the heart from other causes(such as ischemia).As cirrhosis does not normally affect heart function,this complication is often overlooked in practice.In the early stage of CCM,the main manifestations are hyperkinetic circulation.As the disease progresses,patients with CCM show decreased cardiac reserve function.Patients with cirrhosis who have undergone intense acute stimulation such as various surgeries may develop secondary cardiac function problems due to CCM after surgery.Relevant data show that about 50%of patients with cirrhosis will have cardiac decompensation after liver transplantation.In addition,about 20%of patients with cirrhosis also experience cardiac decompensation after transjugular intrahepatic portal shunt,all of which are closely related to CCM.Current studies suggest that compared with healthy people,the serum total bile acid level,especially the hydrophobic component level of bile acid,in patients with cirrhosis changes significantly,and this change,especially in the early stage of cirrhosis,will cause significant changes in the left atrial volume index and cardiac output of patients with high dynamic circulation.As the disease progresses,many factors such as liver function in patients with cirrhosis also change constantly,which may significantly affect the heart function of patients.Therefore,this study intends to analyze the risk factors of CCM and intervene with Ursodeoxycholic Acid(UDCA),a drug that can change the bile acid level and hydrophobic component of CCM model animals,to explore the influencing factors of CCM and effective intervention means.And the mechanism of this mechanism was preliminarily discussed to provide a reliable theoretical basis for protecting the heart function of patients with cirrhosis and reducing the postoperative mortality of patients with cirrhosis.Aims:1.By analyzing the clinical data of patients with cirrhosis,the risk factors of cirrhosis cardiomyopathy were explored in order to provide theoretical basis for the prevention and treatment of cirrhosis cardiomyopathy and protect the heart function of patients with cirrhosis.2.Establish an animal model of CCM,explore the protective effect of UDCA on CCM through animal model tests,and provide effective drugs for the prevention and treatment of CCM.Methods:1.Analysis of risk factors of CCMA total of 1830 patients with cirrhosis admitted to the Department of Gastroenterology of the Second Affiliated Hospital of the Air Force Medical University from January 1,2015 to October 1,2022 were searched through the inpatient management system of Tangdu Hospital.After screening by the inclusion and exclusion criteria,data of 246 patients with cirrhosis were included.Patients were divided into two groups based on the diagnostic criteria of CCM(that is,whether they had systolic or diastolic dysfunction):cirrhosis cardiomyopathy and cirrhotic non-cardiomyopathy.Then,the medical history data between the two groups were compared:(1)baseline data:sex,age,cause of cirrhosis,Child-Pugh grade;(2)Laboratory test results:Aspartate aminotransferase(AST),total protein,albumin,globulin,white sphere ratio,total bilirubin,direct bilirubin,indirect bilirubin,Alanine aminotransferase,ALT),AST/ALT,Serum total bile Acid,international normalized ratio,INR),γ-glutamine transferase,alkaline phosphatase,serum creatinine,prothrombin time,serum Na~+,serum K~+,Model for end-stage liver disease(MELD)score,P<0.05 was considered statistically significant.On this basis,the independent risk factors of CCM were found by univariate and multivariate Logistic regression.2.Study on the effect of UDCA on CCMThe CCM mouse model was constructed by adding 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine(3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-Collidine(DDC)into the feed of C57 mice.The animal experiments were grouped as follows:Normal control group(group A):normal diet was fed for a total of 8 weeks.From the 5th week,50mg·kg-1·d-1 was given intragastric administration for a total of 4 weeks.DDC feed group(Group B):DDC feed was fed for 8 weeks.From the 5th week,50mg·kg-1·d-1 was given intragastric administration for 4 weeks.DDC feed+UDCA intervention group(Group C):DDC feed was fed,and UDCA 50mg·kg-1·d-1 was given intragastric administration from the 5th week for a total of 4 weeks.After modeling,liver cirrhosis of the three groups of mice was observed by HE staining and Sirius scarlet staining.Left ventricular short axis shortening rate of mice in three groups was determined by echocardiography in small animals.LVFS)and left ventricular ejection fraction(LVEF);HE staining and Masson staining were used to observe the cardiac fibrosis of mice in three groups.The serum total bile acid levels of the three groups were measured by biochemical assay.The expressions of farnesoid X receptor(FXR)and takeda G protein-coupled receptor 5(TGR5)in the heart tissues of the three groups of mice were detected by Western Blot.Results:1.A total of 246 patients with cirrhosis were included in the final analysis.According to the results of echocardiography,there were 59 cases in the cirrhotic cardiomyopathy group(23.2%)and 187 cases in the cirrhotic non-cardiomyopathy group(76.8%).Comparison of baseline data showed significant differences in Child-Pugh grade(P<0.001),total bile acid(P=0.001),and serum Na~+(P<0.001)between the two groups.In univariate Logistic regression analysis,we concluded that Child-Pugh grade,alkaline phosphatase,total bile acid,prothrombin time,serum Na~+,albumin and serum K~+levels may be risk factors for CCM,while multivariate Logistic regression analysis showed that:Serum total bile acid concentration(OR:1.007,95%CI:1.000-1.013),Child-Pugh grade(OR:3.644,95%CI:1.814-7.319),serum Na~+(OR:1.232,95%CI:1.117-1.360)is positively correlated with the risk of CCM,and is an independent risk factor for CCM.2.The results of HE and cellophus scarlet staining showed that,compared with the normal control group(group A),the liver of DDC feeding group(group B)and DDC feeding+UDCA intervention group(group C)showed changes such as false lobule formation,fibrous septum formation and connective tissue hyperplasia,and the proportion of fibrosis increased significantly,while there was no significant difference between groups B and C.The results of echocardiography showed that compared with the normal control group(group A),the left ventricular hyperdynamic manifestations of increased LVEF(%)and LVFS(%)occurred in the DDC feed group(group B),but these conditions were reversed in the DDC feed+UDCA intervention group(group C).Massone staining of myocardial tissue showed that the area of cardiac fibrosis in DDC group(group B)was significantly higher than that in control group(group A).Western Blot results showed that the expression of TGR5 in myocardial tissue of mice in DDC feed group(group B)was significantly increased(P<0.05),but after UDCA treatment,the expression of TGR5 in DDC feed+UDCA intervention group(group C)was significantly decreased compared with that in DDC feed group(group B)(P<0.05).Conclusion1.Child-Pugh grade,alkaline phosphatase,total bile acid,prothrombin time,serum Na~+,albumin and serum K~+were the possible risk factors of CCM.Serum total bile acid concentration,Child-Pugh grade and serum Na~+were independent risk factors for CCM.2.The degree of fibrosis in the heart tissue of CCM mice was significantly increased,and the cardiac function was manifested as left ventricular hyperdynamic,which was consistent with the performance of early hyperdynamic circulation of CCM.However,with the intervention of UCDA,the above situation has been significantly improved.This effect may be achieved through bile acid receptors TGR5 and FXR,and the specific mechanism needs to be further discussed. |
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