A Study On Pathological Changes Of Thymus Dendritic Cell Of MODS Mouse And Their Action On Pathogenesis

Objectve:To study the action of dendritic cell on mechanisms of immuneological injury of multiple organ dysfunction syndrome(MODS), which can supply a new pathway in the study of foundation and clinical intervention in MODS and severe trauma infection.Method:Animals: Kunming mice, 6-8 weeks old. Group: healthy control group and exprimental group scheduled to be killed on hour 3, hour 12 to 48 , day 3 to 7, day 8 to 12. Body weight, rectal temperature, behavior of mice, wet organ weight, survival rate, the function of organs were monitored; main organ pathological changes were observed In peripheral blood samples, the content of CD4~T lymphocytes and CD8~T lymphocytes and the ratio of CD4/ CD8 was performed by flow cytometry; Dendriric cells of the thymus recognized by NLDC-145, MJDC-8 and CD1a by means of immunohistochemical method; The expression of Fas/FasL antigen in thymus were detected by means of inimunohistochemical; Apoptotic cells of thymus were detected by means of TUNEL. The ultrastructure of DCs and the tendency of apoptotic cells in thymus were observed. by transmission electron microscope.Result:1. In first 3 hour and 12 to 48 hour, twenty five percent of the animals died; Experimental animals showed significant loss of body weight and temperature; An increase in the serum level of ALT were observed; The content of CD4~T lymphocytes decreased but the ratio of CD4/ CD8 has no changes in peripheral blood samples; Microscope examination of organ tissue showed congestion, edema and several cases showed paracharely cell injury; DC in thymus showed hypertrophy andhyperplasia, their content increased and their function activated; The apoptotic cells increased by means of TUNEL and transmission electron microscope; The expression of Fas/FasL displayed an increase; 2. In the day 3 to 7, five percent of the experimental animals dided. Body weight and tempreture had an ascending tendency. The level of ALT, BUN, CR and CK in the serum, the content of CD4~T lymphocytes and CD8~T lymphocytes and the ratio of CD4/ CD8 , pathologic changes and the content of DC came back to normal level. 3. Eight days after administration of zymosan, animals displayed MODS-like syndromes (tachypnea, cachexia, high mortality rate). The ratio of CD4/ CD8 was invert; All function index increased; The content of DC increased and the function decreased; An increase of apoptotic cells and the expression of Fas/ FasL were observed. The high correlation among dendritic cells, and FasIFasL were observed in MODS course.Conclusion:1. We replicated a delayed model of MODS induced in mice by means of intraperitoneal injection of zymosan. 2 We observed and studyed the figure, the distribution and the content of DC in thymus by means of several specific marker associated labled method and transmission electron microscope technic. 3. We first apply dendritic cell in the study on MODS. The results showed that hyperplasia of DC might be the earliest, and might mediate immunologic regulation and it might be an important factor in MODS course. 4.Hyperactivation of DC and activation of Fas/FasL were one of the important mechanisms which could cause many lymphocytes apototsis and inlmunosupression in MODS.