| Myocardial Infraction has high death rate, seriously threating human survival and death. Currently, reperfusion therapy is usually used clinically. Due to adults’ unable cardiac regeneration and their bad prognosis, dysfunction still exists in the left ventricle. Therefore, it is urgent to find new therapies for renovation after MI. Inflammatory environment after MI is along with the entire process of myocardial renovation, in which moderate inflammatory response can promptly help remove dead myocardial cells and renovate tissue damages.DCs are the most functional antigen-presenting cells in the immune system and important immunomodulatory for innate immune system to start immunoreaction and inflammatory reaction. Researches propose that the number of DCs in rats’ myocardial tissue will increase after the MI. And DCs also appear in people’s infarcted myocardium. The literature review shows that DCs knockout after MI will result in left ventricular remodeling featured by decreased survive rate, thinner ventricular wall, and fibrous degradation. Therefore, it can be inferred that the increased DCs in the myocardial tissues may help the MI damage renovation, but specific mechanisms are not clear yet.Histone acetylation is closely related to gene expression and regulation with the body. Current researches have pointed out that histone acetylation plays an important role in regulating DCs maturation. TSA is a broad-spectrum HDACs inhibitor. Existing researches display that TSA can decrease myocardial infraction areas of rats and ease cardiac function damage, but whether it protects through tissue renovation is to be studied. In brief, TSA can ease cardiac function damage and protect infarcted rats. However, its relationship with DCs and tissue renovation has not been proposed. It is presumed by the author that TSA functions in fibroblasts and damage renovation of myocardial infraction by modulating DCs.Objective: This experiment is aimed to research whether TSA influences DCs and modulates transfer of fibroblasts and collagen synthesis in the damage renovation of myocardial infraction.Methods: Experimental MI model were established in Wistar rats via left coronary artery ligation. TTC staining and the assay of three serum enzyme are used to study TSA’s protective on rats’ myocardial infarction. HE staining was used to observe the effect of TSA on myocardial tissue morphology.OX62 was used as a reliable marker for DCs visualization and to evaluate the dynamic changes, including the numbers of DCs after MI by immunostaining, western blot and Flow Cytometry. Substantially, Immunohistochemical and Sirius staining are used to detect the influence of TSA on transfer of fibroblasts and production of collagen in infracted myocardium, respectively.Results: The results show that in 1d, 3d, 7d, 14 d and 28 d after rats’ infarction the infarcted areas are all on the rise, which is of statistical significance(P<0.001). Compared with the model set, infarction areas of all the different phases show remarkable decreases(P<0.05, P<0.01). The activity of CK, AST and LDH of MI groups are all higher than that of the sham, while these indicators decrease in the TSA-treatment group. The amounts of DCs are higher than the sham in 1d, 3d, 7d, 14 d and 28d(P<0.05, P<0.01, P<0.001) and gradually reach the peak at 7d(P<0.001). After infarction, increased DCs in myocardial tissues are mainly distributed in infarction zones, secondly at the border of infraction zones and rarely in none-infarction zones. The amounts of DCs of the TSA-treatment group all increase and show substantial tendency on the 14 th day with statistical significance(P<0.05, P<0.01, P<0.001). The amount of fibroblasts grows remarkably since the 7th day after myocardial infarction and further increases in 14 d. Compared with the MI group, the amounts of fibroblasts are all on the rise in 1d, 3d, 7d, 14 d and 28 d after MI, showing statistical significance(P<0.05, P<0.1, P<0.001). In 1d, 3d, 7d, 14 d and 28 d after MI collagen expression increases with time and it shows substantial increase in 3d. Collagen expressions in myocardial tissues of the TSA-treatment group remarkably increase compared with MI model set, showing statistical significance(P<0.05, P<0.01).The influence of TSA on transfer of fibroblasts and the expression of collagen of rats was enhanced greatly.Conclusions: 1. After infarction the quantity of DCs are gradually rising in 1d、3d、7d, further reaching the top at 7d.2. TSA can increase the amount of OX62+cells. TSA can increase DCs.3. TSA can promote transfer of fibroblasts and production of collagen. Number of fibroblasts and collagen deposition modulated by TSA may have relationship with the increase of DCs for renovation after myocardial infarction. |
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