| Objective:Restenosis(RS) remains the principal problem in percutaneous corona-ry intervention (PCI) treatment.Inflammation mechanism is one of the major core mechanisms in the formation of ISR, and it plays an important role in intima hyperplasia and restenosis. TLR4-NF-κB signal pathways may be involved in the inflammatory reaction, promote vascular smooth muscle cells(VSMCs)proliferation and lead to intima hyperplasia and restenosis. Therefore, to intervene the inflammatory reaction net will become the effective measure to prevent restenosis. With the development of modern medicine research on pathogenesis of IRS, traditional Chinese medicine puts forword "toxicity and stagnation interties inside artery " is the key factor causing IRS."Toxicity and stagnation interties inside artery" theory is highly similar to ISR inflammation mechanism.For this purpose,this study adopts both clinical and experimental research ways, from the whole and the microscopic two angles,from clinical biochemical and cellular and Mo-lecular level two levels.This research attempts to systematically study the changes happened on the patients who have received PCI operations, for exmple, peripheral blood nuclear factors, kappaB(NF-KB), IL-1, TNF-α and the relationship between postoperative events and ISR, thus to illuminate the clinical efficacy and safety of the detoxifying.At the same time, we will establish the rat thoracic artery restenosis model and display how the detoxifica-tion and activating blood circulation therapy intervenes the inflammatory reaction and then inhibits VSMCs migration and proliferation to hold back intima hyperplasia and prevents restenosis through adjusting TLR4-NF-κB signal transduction pathways. This study exerts the diagnosis and treatment of traditional Chinese medicine and supplies the scientific basis for the clinical applications of the therapy.Methods:This research is divided into document studies and clinical studies. In clinical studies, select40patients as the standard PCI postoperative subjects, based on the PCI postoperative treatment as the control group and the PCI postoperative treatment+the detoxification and activating blood circulation therapy as the treatment group. In each of the two groups, there are20subjects (n=20).Then, select20cases of hospitalized patients of the corresponding time with normal coronary angiography as the normal group. Make an analysis of the NF-κB, IL-1and TNF-α levels of the two groups of patients preoperative and post operative24hours or14days. Observe the cardiovascular events and in-stent restenosis, occurring on the patients within6months after the operation and so on and so forth.In animal studies, imitate the theory of PCI postoperative restenosis, and establish the model of rat thoracic artery restenosis, which shares the pathological features similar to that of the vascular restenosis.Measure the proportion of inflammatory factors in plasma and vascular tissues, such as IL-1, TNF-α、MCP-1and ICAM-I, and test the rate of proliferation of VSMCs, the protein expressions of TLR4、NF-κB、κBαin vascular wall cells. Make use of the detoxification and activating blood circulation therapy through the route of signal transduction pathways of TLR4-NF-κB to intervene the inflammatory reaction, inhibit VSMCs proliferation and prevent restenosis.Results:1. Detoxification and Activating Blood Circulation Therapy of Plasma in Patients with PCI Postoperative NF-κB Activity and the Influence of In-stent RestenosisAs for the two groups of patients, NF-κB activity rises significantly before PCI operation compared with the control group, NF-κB activity level is significantly increased in postoperative24hours compared with that before operation(P<0.01); in the treatment group, the patients’ NF-κB activity decreases significantly in PCI postoperative14days compared with the control group (P<0.01);In the treatment group, the occurrence of cardiovascular events and the incidence of restenosis within6months after PCI is significantly lower than that of the control group (P<0.05).2. The Establishment of the Rat Thoracic Artery Restenosis ModelIntima thickens in14days, and a large number of hyperplastic VSMCs in disorder with circular and oval nuclei is seen; the endothelium continues to proliferate within28days, the ECM increases, and then the thickness of the neointima differs, and finally the restenosis becomes serious. This indicates the typical animal model of vascular restenosis is formed.3. The Influence of Detoxification and Activating Blood Circulation Therapy on the Hyperplasia VSMCs of the Rat Thoracic Artery after Balloon Damage3.1The proportion of inflammatory factors in plasma and vascular tissues, such as IL-1, TNF-α,MCP-1and ICAM-I in model group, the detoxification and activating blood circulation therapy big, average and small amount groups and asprin group increases obviously (P<0.01). After treatment, in the detoxification and activating blood circulation big, average and small amount groups and asprin group, the level of inflammatory factors evidently decreases (P<0.01)3.2The protein expressions of PCNA, CyclinDl, Cyclin in vascular tissues become enforced. In the detoxification and activating blood circulation therapy big, average and small amount groups and asprin group, PCNA, CyclinDl, CyclinE protein amount in the proliferated endothelium can be reduced, VSMCs hyperplastic rate can be lowered and cell cycle control can be improved.3.3Use western blot method to measure the protein expressions of TLR4, NF-κB p65, IκBα in vascular tissues. In the detoxification and activating blood circulation therapy big, average and small amount groups and asprin group, the protein expressions of TLR4,NF-κB p65can also be reduced, but the protein expressions of IκBα rise compared with that in the model group.Conclusions:1. The detoxification and activating blood circulation therapy can effectively reduce the activity of NF-κB and the level of IL-1,TNF-αin plasma, thus restrain the inflammatory reaction, reduce clinical symptoms and the degree of ISR.2. Successfully establish the rat thoracic artery restenosis model.3. The proportion of IL-I, TNF-α, MCP-1, ICAM-I, VCAM-1in plasma and vascular tissues after PCI operation rises distinctly and The detoxification and activating blood circulation therapy can functionally lower the level of inflammatory factors, thus inhibit VSMCs proliferation and intima restenosis.4.The detoxification and activating blood circulation therapy can reduce the amount of protein of PCNA, CyclinD1, CyclinE in vascular tissues. This suggests the therapy can restrain the activity VSMCs proliferation and improve cell cycle control.5.The high rate of expression of signal pathways of TLR4-NF-κB on the partial tissues after PTCA operation; the detoxification and activating blood circulation therapy through the route of signal transduction pathways of TLR4-NF-κB can intervene the inflammatory reaction, inhibit VSMCs proliferation and alleviate intima restenosis. This thesis attempts to clarify the physiopathologic mechanisms of the detoxification and activating blood circulation therapy which can be used to intervene IRS. |
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