| BackgroundChronic heart failure is the end stage of many cardiovascular diseases and is characterized by abnormalities in the structure and / or function of the heart.Heart failure is a disease state in which the chronic immune system is activated,suggesting insufficiency of normal immunomodulatory mechanisms.Both Th17 cells and Treg cells are derived from naive Th cells and have opposite effects,playing an important role in immune response and regulation.Th17/Treg balance is involved in the pathological process of heart failure,and maintaining the relative balance of the two can delay the occurrence and development of heart failure.In preclinical trials,Yiqi Huoxue Recipe can relieve patients' clinical symptoms,improve patients' quality of life,and have significant clinical efficacy.However,whether Yiqihuoxue recipe can improve myocardial remodeling by increasing the endogenous protective cells or inhibiting the two-way regulation of the immunoregulatory inflammatory response of inflammatory cells,it is worth studying in depth.ObjectiveIn this study,a rat model of chronic heart failure was established wit h left coronary artery ligation,to observe the effect of Yiqi Huoxue recipe on rats with chronic heart failure,study the role of Th17/Treg cell imbalance in the occurrence and development of CHF,and further explore the effect mechanism of Yiqi Huoxue recipe on chronic heart failure rats from the PD-1/PD-L1 pathway.MethodThe SD rat left coronary artery ligation model was used as the research object,evaluate the heart failure model 4 weeks after surgery,and divide the successfully prepared rats into sham operation group,model group,captopril group,yiqihuoxue recipe low-dose group,yiqihuoxue recipe middle-dose group,yiqihuoxue recipe high-dose group,the intervention rats were given for 8 weeks.Color Doppler ultrasound examination of rat heart structure and function,Serum NT-pro BNP test to evaluate the degree of heart failure in rats,Masson staining to observe myocardial injury,HE staining to observe the pathological changes of spleen tissue,flow cytometry to detect the level of th17 and treg cells in the spleen,Immunofluorescence staining to detect the expression level of th17 and treg positive cells in rat myocardium,and ELISA detection of serum IL-10,IL-17,RT-PCR and Western Blot were used to detect the expression of PD-1 and PD-L1 genes and proteins in the heart.Result1 Compared with the sham operation group,the model group had significantly lower EF(P <0.01),significantly lower FS(P <0.01),and significantly lower IVSd and IVSs(P <0.01 or P<0.05),LVIDd and LVIDs increased significantly(P<0.05 or P<0.01),NT-pro BNP increased significantly(P<0.01);a large amount of blue collagen fiber deposition in the myocardial infarction area,and the marginal fibrosis area of the infarction area was large;the spleen of the model group was congested,the tissue structure changed,and the red and white pulp was unclear.Compared with the model group,the captopril group and the Yiqi Huoxue Recipe group can increase the EF and FS values to different degrees(P<0.01 or P<0.05),improve the thickness of IVSd(P<0.05),and reduce LVIDs(P<0.05),reduce the serum NT-pro BNP level(P<0.01),reduce the myocardial fibrosis level,improve the pathological damage of the spleen to varying degrees,and delay myocardial remodeling.2 Compared with the sham operation group,the percentage of spleen Treg cells in the model group was significantly reduced(P<0.05),the expression of myocardial CD25+FOXP3 positive cells was reduced(P<0.05),the serum IL-10 level was significantly reduced(P<0.01),and the spleen Th17 The percentage of cells increased significantly(P<0.05),the expression of myocardial CD4+IL-17 positive cells increased(P <0.01),the level of serum IL-17 increased significantly(P<0.05),and the ratio of Th17/Treg cells increased significantly High(P<0.05),P<0.01);compared with the model group,the captopril group and Yiqihuoxue prescription groups can increase the percentage of rat spleen Treg cells to varying degrees(P<0.05),myocardial CD25+FOXP3 positive cell expression increased(P<0.01),increased serum IL-10 level(P<0.01 or P<0.05),decreased spleen Th17 cell percentage(P<0.05),myocardial CD4+IL-17 positive cell expression reduced(P<0.01 or P <0.05),reduce the level of serum IL-17(P <0.01),reduce the Th17 / Treg cell ratio(P <0.01 or P <0.05).3 Compared with the sham operation group,the PD-1m RNA and PD-L1 m RNA in the myocardium of the model group were significantly reduced(P<0.01),and the protein expression levels of PD-1 and PD-L1 were significantly reduced(P<0.01).Compared with the model group,the captopril group and each group of Yiqihuoxue recipe can increase the level of PD-1m RNA and PD-L1 m RNA(P<0.01 or P<0.05),elevate PD-1,PD-L1 protein expression level P <0.01 or P <0.05).Conclusion1 Yiqi Huoxue Recipe can effectively improve the cardiac function of rats with chronic heart failure after myocardial infarction,reduce the level of myocardial fibrosis,and delay ventricular remodeling.2 Yiqi Huoxue Recipe can improve the imbalance of Th17/Treg cell ratio by increasing Treg cells,reducing the level of Th17 cells,thereby regulating immune-mediated inflammation in both directions,and thus improving myocardial remodeling.3 Yiqi Huoxue recipe can regulate the Th17/Treg immune imbalance in the chronic heart failure rat,and its mechanism may be related to the regulation of the immune function of PD-1/PD-L1 pathway. |
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