2002 Fiscal Year Final Research Report Summary
The mechanisms of lymphocyte apoptosis after surgical stress
| Project/Area Number |
11671194
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Osaka Medical College |
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Principal Investigator |
HIRAMATSU Masako Osaka Medical College Faculty of Medicine Assistant Professor, 医学部, 講師 (80309153)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGAWA Nobuhiko Osaka Medical College Faculty of Medicine Professor, 医学部, 教授 (00111956)
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| Project Period (FY) |
1999 – 2002
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| Keywords | Surgical stress / Apoptosis / Lymphocyte / Endotoxin |
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| Research Abstract |
1. The induction of lymphocyte apoptosis in murine models of sepsis
After intraperitoneal administration of LPS, apoptosis was observed only in the thymus. When the mice was challenged with CLP (Cecal Ligation and Puncture), apoptosis was observed not only in thymus but also in spleen, lung, and Peyer's patch of gut of both strains, C3H/HeN and C3H/HeJ. The data suggest the existence not only of and endotoxin-driven activation for thymic apoptosis, but also of an endotoxin-independent, TNF-independent pathway activating widespread apoptosis in the murine CLP model of sepsis.
2. The induction of lymphocyte apoptosis in murine models of hemorrhagic shock
In murine hemorrhagic shock/Resuscitation (HEMS) model, apoptosis was induced in thymus, spleen and Peyer's patch of gut, same as in CLP model. Apoptosis in spleen and gut were controlled by SOD and Mn-TBAP which is low molecular SOD mimetic.
3. The induction of lymphocyte apoptosis after surgical stress
The estimation of lymphocyte subset resulted that the number of CD4 positive cell was decreased in the patients underwent major surgery. Apoptosis assay of peripheral lymphocyte and lymphoid tissue demonstrated that lymphocyte apoptosis was induced by major surgical stress. Similar result was obtained in the septic patients.
To study the therapeutic significance of PMX in patients with intra-peritoneal sepsis, apoptosis assay was also performed before and after hemoadsorption by PMX. Lymphocyte apoptosis was not inhibited by endotoxin removal by PMX, though the mortality of the most critical patients with colorectal perforation was improved.
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