The Role Of TIMP-1 In Myocardial Fibrosis Of Rat And Its Relationship With Apoptosis

The body's cells destined to die, Part of death is due to physiological, Another part of the death was due to pathological, At present the process of cell death, in recent years has become a biology, medical research in the field of a hot topic. Far, to, people have to know the way of cell death at least two ways: Namely necrosis and apoptosis. Cell necrosis has been recognized as early as a way of cell death.The cells are gradually being recognized by the recent years, a cell death.Apoptosis is a basic biological phenomenon cells. Its evolution in the organism, homeostasis and the development of a number of systems plays an important role. Apoptosis is not only a special kind of cell death, But also has important biological significance and the complex molecular mechanisms. Over time, growing recognition of biological cells is the growth of various cells, development and normal life activities play a more important role. Also found that the incidence of many diseases and apoptosis is closely related to the imbalance. It is not only the basis of cell died of natural causes, but also to embryonic development, hematopoiesis, immune, and the incidence of such tumors. Apoptosis became the order of today's life science research areas of concern to many scholars.A distinct feature of apoptosis is cell chromosome DNA, which is a relatively common phenomenon. Such degradation of very specific and regular, the length of the DNA fragments generated approximately integer multiples of 180-200bp, which is winding the length of histone oligomers.In addition, Apoptosis is tightly controlled by the process of multiple genes. These genes are very conservative species, such as Bcl-2 family, caspase family, such as C-myc oncogene, tumor suppressor gene P53, etc. With the development of molecular biology techniques to thousands of the process of apoptosis has been very in-depth understanding. But so far the exact mechanism of apoptosis has not yet fully understood.The present study suggested that TIMP had the role of cytokines like and induced apoptosis through signal transduction pathways. With non-invasive diagnosis of fibrosis indexes in-depth study, Some new indicators, such as MMP-1 and TIMP-1 had received extensive attention. The experimental study found that The metabolism of ECM regulated by MMPs and related inhibitors TIMPs. Which degrade ECM components (I, III collagen) and MMP-1 and related inhibitors of tissue inhibitor of matrix metalloproteinase-1 is considered to play a key role. In addition tissue inhibitor of matrix metalloproteinase-1 lymphoma cells by autocrine or paracrine generated, By the B cell growth and differentiation factor IL-10 and the proto-oncogene Bcl-xL to inhibit the process of apoptosis, extended from the normal tonsil B cells, Burkitt lymphoma cell lines of life, treatment by the alkylating agent loss of inhibition of MMP tissue inhibitor of matrix metalloproteinase-1 also has anti-apoptotic effect.Myocardial fibrosis refers to excessive accumulation of collagen, the collagen concentration increased significantly. The experimental study found that apoptosis in myocardial fibrosis found in various kinds of heart disease. Virus infection, high blood pressure, heart disease and superoxide MF arising under the process, apoptosis involved. To sum up the above arguments, MF is a class of complex pathological process involving the RAAS system, the immune system and a variety of cytokines involved in inflammation, apoptosis, and cell signal-regulated Dengjun its occurrence.The drug of catecholamines contained Epinephrine, Noradreline and Iso. They could cause Multiple foci of myocardial necrosis and Subsequent MF. The drug of catecholamines could cause Adaptive hypertrophy of cardiomyocytes Cardiomyocyte apoptosis and Shorten the life span of myocardial cells. It could cause Apparent proliferation of interstitial collagen and induced Interstitial fibrosis. The study found that Iso can alleviate myocardial hypertrophy and fibrosis. As such myocardial damage modeling method is simple, Reliable results and MF indeed the pathogenesis of the involvement of catecholamine drugs, so Iso in the MF study has important value.In this experiment, the rat's myocardial model was copied by using a One-time multi-point subcutaneous injection 10mg/kg body weight Iso method induced rat's Myocardial necrosis model. Then HE staining, immunoh-istochemistry and RT-PCR determinated TIMP-1, Bax expression. To investigate 10mg/kg body weight Iso induced myocardial injury degree, and the role of TIMP-1 in myocardial fibrosis and relation with cell apoptosis. These ex-perimental result may be the prevention, Diagnosis and treatment of many diseases provided Important clinical basis.The results of immunohistochemistry. 1. Detection of morphology The necrosis, apex, endocardial, and perivascular could see obviously myofibrillar fragmentation of structure at 12h, there is inflammatory cell infiltration, and the formation of solidification muscular dissolved. With the prolong of injection time, the necrosis area increased and found more fibrosis at 3w.2. Bax expression The expression of Bax is a few in normal rat's myocardium, With the prolong of injection time, its expression increased significantly at 3 w and reached the maximum. The TIMP-1 was weakly positive expression in control. With the prolong of injection time, its expression arrived the maximum at 72h (P<0.01). TIMP-1 expression decreased gradually at 1 w and arrived a minimum at 3w.3. Bax mRNA expression arrived a peak at 12h as compared with control (P<0.01), and its gene expression decreased gradually at 24 h later.4. The ratio of TIMP-1/Bax decreased with prolong Iso injection time and arrived a peak at 12h.The main conclusion of this research:1. One-time multi-point subcutaneous injection 10mg/kg Iso could encourage a large number of TIMP-1 expression, arrived a peak at 72h and reduced gradually at 1 w. These results illuminated that the role of TIMP-1 on Inhibition of apoptosis was maximum at 72h. The role of TIMP-1 on Inhibition of apoptosis reduced gradually at 1 w later. One-time multi-point subcutaneous injection 10mg/kg Iso could encourage a large number of Bax expression, thus contributing to apoptosis. Bax mRNA expression arrived a peak at 12h as compared with control (P<0.01), and its gene expression decreased gradually at 24 h later. 2.The ratio of TIMP-1/Bax and mRNA expression arrived apeak at 12h, Suggest inhibition of apoptosis may be carried out simultaneously.