The The SIRS-lung Injury In Rats Model With Anti-inflammatory Factor Expression And AP-1 Activity Change

Systemic inflammatory response syndrome (SIRS) is a clinical process of systemic widespread inflammatory reaction caused by various severe injuries, especially trauma and infection etc. Severe trauma and infection are common causes for occurrence of SIRS. Meanwhile, the infection secondary to primary diseases often aggravates SIRS, resulting in rapid exacerbation of the diseases. The uncontrolled development of SIRS will surely causes MODS or MOF. In the lungs, SIRS is represented by acute lung injury (ALL) that will develop into acute respiratory distress syndrome (ARDS). Therefore, SIRS is the common pathogenic basis for ALI/ARDS as well as MODS/MOD. Up to now, the mechanism for occurrence of SIRS has not been clarified. Some researchers believe that it might be associated with disorder of cytokine network. SIRS is the result of not only excessive production and release of inflammatory mediators but also abnormality in production and release of internal anti- inflammatory mediators. Excessive production and release of internal anti- inflammatory mediators such as anti-inflammatory cytokine etc. may play an important role in pathogenesis of SIRS. Interleukin-4 (IL-4), IL-l0 and IL-13, which are important internal anti- inflammatory cytokines, are closely related to recovery of SIRS. AP-1, a nuclear transcripton is associated with production of many cytokines. LL-4, IL- 10 and IL- 13 can affect activity of AP- 1. In addition, activation of AP- 1 can change expression of their genes because there are binding sites of AP- 1 in III k .~ modulating sequence of their genes. Nowadays, the state of anti-inflammatory factor of SIRS and its relation to the transcripton remain unclarified. In this study, SIRS-pulmonary injury models of injury inflicted by using gradient-dosage LPS once and injury inflicted by using OA+LPS twice were established by employing LPS and OA in Wistar rats. Then contents of plasma LL-4, IL-10 and IL-13 were determined with ELISA, levels of IL-4, LL-10 and IL- 13 mRNA in pulmonary tissue with RT-PCR and AP- 1 activity in the pulmonary tissue with EMSA. Furthermore, ELISA was employed to determine contents of plasma IL-4, IL- 10 and IL- 13 in patients with ARDS and SIRS. Results: 1) When the dosage of LPS was equal to or over 6 mg/kg, Pa02 in the early stage was less than 8kPa, WBC counts in peripheral blood increased and then decreased, the composing ratio of large WBC significantly increased, water content in the lungs increased and pulmonary pathological changes aggravated in the rats. 2)In those rats with pulmonary injury inflicted by using OA+LPS twice, Pa02 was significantly decreased, WBC counts in peripheral blood and the composing ratio of large WBC markedly increased, water content in the lungs increased. These changes were the most remarkable in those rats with pulmonary injury inflicted by using OA+LPS twice at an interval of 4 hours.3) In the rats with pulmonary injury inflicted by using gradient-dosage LPS, the contents of plasma IL-4, IL-10 and IL-13 as well as their mRNA in pulmonary tissue were significantly increased, AP- 1 activity in lung tissue enhanced. At a dosage of LPS ~6 mg/kg, the time for achievement of the peak values of contents of plasma IL-4, IL- 10 and IL- 13 was brought forward to the 2nd hour. The peak values of the contents of plasma IL-4, IL- 10 and IL- 13 as well as their...