| The pathogenesis of endotoxin-induced acute lung injury remains obscure and hasn`t been fully elucidated hitherto. It is well known that the uncontrolled systemic inflammatory response is an important mechanism for acute lung injury. Studies in recent years show that there is a widespread apoptosis of lymphocytes and parenchymal cells in tissues and organs including lung during sepsis. It is considered that apoptosis may represent a key factor in modulating the balance between inflammatory and anti-inflammatory response during systemic inflammation. CD4+ T lymphocytes play a pivotal role in immune response and its regulation, and they act as important effector cells as well. CD4+ T cells include two types, Th1 and Th2. Th1 cells secret inflammatory factors including TNFα,TNFβ,IL-2 and IFN-γ , being closely related to T cell-mediated inflammation, whereas Th2 cells synthetize some anti-inflammatory factors, such as IL-10 and IL-4, thus down-regulating inflammatory response in vivo. Much evidence demonstrate that lymphocytes experience apoptosis during ALI or ARDS. However, it is poorly described that whether the apoptosis of Th1 cells and Th2 cells occurs synchronously and equivalently, as well as the effects of Th1,Th2 apoptosis on the development of ALI or ARDS. Thus, we develop the lipopolysaccharide-induced lung injury model in rats to investigate the following: (1)the apoptosis of CD4+T lymphocyte in peripheral blood and BALF; (2)apoptosis of Th1 cells and Th2 cells in peripheral blood and in BALF detected by combination of immunohistochemistry analysis and TUNEL; (3)effects of dexamethasoneon Th1,Th2 cells apoptosis; (4)the relationship between Th1,Th2 apopotosis and lipopolysaccharide-induced lung demage. The aim of this study is to provide some laboratory evidence and a potential theoretical basis at the point of Th1/Th2 drift in order to improve the understanding of the molecular mechanism for anti-inflammatory response and inflammatory response. The main results and conclusions are shown as follows: 1. After LPS challenge, the percentage of CD4+ T cells in peripheral blood and in BALF was gradually decreasing as compared with that of normal control (34.82+/-1.71% at 6h time point and 31.02+/-2.52% at 24h time point vs 58.67+/-5.93% in peipheral blood; 30.76+/-3.03% at 6h time point and 28.80+/-2.57% at 24h time point vs 47.31+/-2.22% in BALF; P<0.01). The relative analysis showed a significant negative correlative relationship between the percentage of CD4+T cells and proportion of the apoptotic cells among them, indicating that the number of CD4+T cells decrease in time-dependent manner because of apoptosis. Comparied with LPS group, no significant difference exists in DEX group. 2. The number of IFN-γ positive cells(Th1) and IL-4 positive cells(Th2) in peripheral blood and in BALF decrease after LPS challenge. There is a negative corelative relationship between the percentage of Th1 cells(24.1+/-2.1% at 6h time point vs 49.8+/-1.9% in peipheral blood; P<0.01 and 31.9+/-1.5% at 6h time point vs 49.1+/-2.1% in BALF；P<0.01) and apoptotic cells among them, indicating the reduction of Th1 cells is associated with apoptosis. While the constituent ratio of Th1 cells rises initially and then decreases, the constituent ratio of Th2 cells increases continouslly, indicating that apoptosis makes CD4+T cells drift from Th1 to Th2. The numbers of IFN-γ positive cells and IL-4 positive cells decrease in dexamethasone(DEX) group. The percentage of apoptotic cells among IL-4 positive cells increases significantly, and there is a remarkable difference between the DEX group and the salinecontrol group. By comparison, the raising level of the percentage of IL-4 positive cell apoptosis is lower. These results all indicate that DEX can adjust the ratio of Th1/Th2 to a normal level by regulating inflammatory reaction. The reduction of lymphocytes is closely relative to apoptosis, which may be one of the causes for imbanlance of inflammatory reaction and anti-inflammatory reaction in lipopo...
|
PDF Full Text Request