Change Of TNF-α,IL-6,IL-23 Levels From Patient Unstable Angina Pectoris And The Effect Of Fasudil

Unstable angina pectoris (UAP) is a group of clinical angina syndrome,which between chronic stable angina pectoris (SAP) and acute myocardial infarction (AMI),and UAP is one of common clinical emergency. Pathogenesis and pathomechanism of UAP is mainly rupture of coronary AS plaque,aggregation of platelet,the coagulation of blood by tissue factor,obstruction of thrombi,further narrow of the blood vessel,and leading to increased myocardial ischemia. Among them,instability and rupture of coronary plaque are the main reasons for arises of UAP. Recent studies have shown that in instability plaque infiltration of a large number of inflammatory cells,including macrophages,T lymphocytes and mast cells. They can damage the endothelial cells and promote aggregation of platelet and thrombosis, which resulting in contortion and narrow of vascular cavity eccentric circle. So scholars think that the infiltration of inflammatory cells and inflammatory mediator of their secretion in AS plaques,especially the interaction and synergy of local cytokines,is an important factor to determine whether plaque ruptures,thus becoming the focus of prevention of plaque rupture.Both TNF-αand IL-6 are inflammatory cytokines,and they have a variety of performance and very extensive role. A large number of basic and clinical trials indicate that both are involved in the whole process of the occurrence and development in UAP,suggesting that to some extent stability of AS plaque can predict the long-term cardiovascular events. IL-23 is one kind of cytokines which is composed of P19 subunit and P40 subunit,and it mainly comes from activated mononuclear macrophages and dendritic cells. Studies have confirmed that IL-23 is involed in many pathological processes,such as spontaneous arthritis,rheumatoid arthritis,inflammatory bowel disease,chronic obstructive pulmonary disease,cancer and so on. Since IL-23 mainly acts on T cells,DC,and monocyte-macrophage cells,while the above-mentioned three kinds of cells play an important role in occurrence and development of AS plaque in UAP patients,so we speculated that IL-23 is involved in the entire process of formation and rupture of the AS plaque through the above channels.Fasudil is a novel isoquinoline sulfonamide derivative,which plays a pharmacological effect mainly by inhibiting ROCK and commonly used in the treatment of cerebral vascular diseases. By the relevant data,fasudil may be better efficacy in patients with UAP,but its mechanism of action is not clear. So we make further efforts to explore that fasudil acts on the UAP by anti-inflammatory response and inhibiting level of inflammatory cytokines.Now few people explore the relation between TNF-αand IL-6 and disease severity from the perspective of risk stratification about UAP,moreover,it is less report that fasudil acts on serum levels of TNF-αand IL-6 in the UAP patients,it is little report that IL-23 is involved in the pathogenesis of UAP, fasudil acts on serum levels of IL-23 and exploring the correlation between IL-23 and disease severity from the perspective of risk stratification in UAP patients. Thus if our test succeed,it may not only confirm inflammation in UAP patients, and to some extent level of inflammatory cytokines in Peripheral blood may be the index to reflect stability of AS plaque and predict cardiovascular events,but also it may provide experimental basis for controlling inflammatory response through blocking cytokine for the clinical pathway and prevention and treatment of UAP. The study will have better economic and social benefits.ObjectiveTo study role of cytokines TNF-α, IL-6 and IL-23 in UAP patients and the effect of fasudil on these cytokines.MethodAccording to patient's medical history, clinical symptoms , laboratory tests ,electrocardiograms,X-ray and cardiac ultrasound and other tests,patients were divided into UAP group and SAP group. Which,UAP group was 60 cases including 36 males and 24 females,and SAP group was 20 cases including 12 males and 8 females. Referencing to medical history,pain characteristics,clinical manifestations,ECG and measurement results of cardiac markers in patients with UAP,patients of UAP group were divided into low-risk,medium-risk and high-risk group. 20 patients of low-risk group included 13 males and 7 females,and 20 patients of medium-risk group included 11 males and 9 females,and 20 patients of high-risk group included 12 males and 8 females.While 20 cases of healthy adults as normal control group,in which including 15 males and 5 females. The UAP group match was divided into:conventional therapy group and the fasudil treatment group,and they were 30 cases eath. UAP patients were conventionally treated with extended crown (isosorbide mononitrate injection-Isosorbide Dinitrate),anticoagulation (thanks to aspirin,low molecular weight heparin-Bo Pu blue),lipid-lowering (atorvastatin- Lipitor) and so on,and taking sublingual nitroglycerin tablets as angina attack. Fasudil treatment group used fasudil injection additioonally,and intravenous injection with normal saline 50mL including 2mL of the drug,2 times a day,course of treatment 14 days. Before all cases were selected and after UAP patients were treated we took the elbow vein in the early morning to separate serum and preserve it at -80℃refrigerator. We tested the level of serum TNF-α,IL-6,IL-23 by taking ABC- ELISAP method of double-antibody sandwich.ResultsUAP group pre-treatment serum TNF-α,IL-6 and IL-23 were higher than SAP group and normal control group (P<0.01),SAP group pre-treatment serum TNF-α,IL-6 and IL-23 were slightly higher than the the normal control group (P<0.05). Before treatment in the UAP group,the levels of serum TNF-α,IL-6 and IL-23 in high-risk group were higher than that in medium-risk and low-risk group (P<0.01),the levels of serum TNF-α,IL-6 and IL-23 in medium-risk were higher than that in low-risk group (P<0.05).Fasudil treatment group after treatment serum TNF-α,IL-6 and IL-23 compared with before treatment were significantly lower (P<0.01). Conventional therapy group after treatment serum TNF-α,IL-6 and IL-23 compared with before treatment were lower (P<0.05). Fasudil therapy group after treatment serum TNF-α,IL-6 and IL-23 compared with the conventional treatment group after treatment were lower (P<0.05).Conclusion1. Abrupt increase of TNF-α,IL-6 and IL-23 expression level in Peripheral blood can prompt inflammatory response in UAP.2. Expression level of TNF-α,IL-6 and IL-23 in Peripheral blood can be used as an indicator of plaque stability in UAP. 3. TNF-α,IL-6 and IL-23 can as a sensitive indicator to reflect degree of disease severity.4. Fasudil can inhibit increase of TNF-α,IL-6 and IL-23 in patients of UAP.5. As a novel anti-inflammatory drug fasudil can apply the treatment of UAP.