| Objectives:Heart transplantation has become the most effective therapy for end-stage heart disease. The function of heart graft determined not only the clinical manifestation of patients, but also survival quality and times. Recently, with the development of Biotechnology, the researches of apoptosis have been carried on all over the world, and a large number of clinic and laboratory outcomes had indicated that apoptosis was one of the most important way of cell death in heart graft. Apoptosis in mammals was executed by cysteine-containing aspartate-specific protease (Caspase or Casp) families and endogenous nuclease (DNase). In human, the activation and over expression of caspases can bring about cell apoptosis not only by destroying cell structure directly, but also by inactivating apoptosis inhibitors (for example, bcl-2) and producing the apoptosis-inducing fragments at the same time. Study also showed that caspases could cause DNA fragmentation by cleaving the inhibitors of endogenous nuclease (DNase), indicating that caspases families was the crucial molecular groups which could cause cell apoptosis, and caspase-3 was the key effective enzyme, the executor of cell apoptosis. It had already been accepted that the main pathological processes, such as ischemia-reperfusion injury or rejection, hadclose relation to apoptosis and its genetic regulations. Caspases activated by internal or external causes could lead to cell death through DNA rupture, chromatin condense and the wreck of cell framework. Selective and non-selective caspases inhibitors all could inhibit apoptosis in different approaches.A great deal of experiments indicated that element-trace zinc could inhibit the activation of caspase-3 through different approaches in different tissue. But the study on the protective effect of element-trace zinc on cell apoptosis in heart graft by inhibiting caspase-3 has not been reported in our country. The improved Ono rat heart transplantation models are administrated with different dosage of ZnSO4. We observe the apoptosis condition, detecte the expression of caspase-3 and measure the survival time of the heart graft. Consequently, by discussing the anti-apoptosis effects of ZnSO4 in rat heart transplantation model, we can provide theoretical evidence for the clinical practice of this agent. Methods:Adult healthy clean inbred strain closed clone rat were chosen, the range of their weight was 280?0g. A rat heterotopic cardiac transplant model with Wistar recipients and SD donors was used. Group A : SD to Wistar rat heart transplantation, treated with physiological saline injection peritoneum twice daily; Group B: SD to Wistar rat heart transplantation, treated with 0.5% ZnSO4(2mg/kg) injection peritoneum twice daily; Group C: SD to Wistar rat heart transplantation, treated with 0.5% ZnSO4 (5mg/kg) injection peritoneum twice daily. Statistical analysis:We used SPSS 10.0 to analyze the data. Results were expressed by a <0. 05 was regarded as the level of test. Results:1. The apoptotic cell in cardiac allograft: on postoperative day 4th, apoptotic cell in each group were detected. There were significant difference between groups (P<0.05).Compared with group A and group B, the apoptotic cell of graft tissues in group C reduced significantly by administering with 0.5% ZnSO42. Similarly, there were significant difference of caspase-3 expression between groups. Compared with group A and group B, the expression of caspase-3 in group C reduced significantly (P<0.01).3. The mean survival times in each group also had significant differences (P<0.01). Allograft survival exhibited a dose-dependent relationship with ZnSO4 .4. There was a positive correlation between AI and CEI of myocardic cell in heart graft (r=0.808, PO.01) . This indicated that caspase-3 was closely related to cell apoptosis.Conclusions:1. The apoptosis in heart graft increased with the rise of caspase-3 positive expression. There is apositive correlation between apoptosis index (AI) and caspase-3 expression index (CEI) of myocardiac... |
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