2003 Fiscal Year Final Research Report Summary
Research on mechanism of apoptosis and organ damage after hemorrhagic shock and resuscitation
| Project/Area Number |
14571461
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Nara Medical University |
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Principal Investigator |
MURAO Yoshinori Nara Medical University, associate professor, 医学部, 助教授 (50211602)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Hemorrhagic Shock / Hypertonic Saline / Apoptosis / TUNEL / DNA ladder / Caspase-3 / HSP 70 / HSP 40 |
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| Research Abstract |
Male BALB/c mice were hemorrhaged to the mean arterial pressure of 40+/-5 mmHg for 90 min. Resuscitation was made by 4ml/Kg of 7.5% NaCl (hypertonic saline; HS) and shed blood (SB) or two times the volume of shed blood (2LR+SB) +SB or sham (catheter only) or control (no treatment).
(Small intestine) Intestinal injury was devised and based on the extent of the vacuolation at basal area of the intestinal villi. Apoptosis score of the small intestines were examined by terminal deoxynucleotidyl transfer-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) methods and DNA ladder assay. Activation of caspase-3, HSP 70, HSP 40 expression were assessed by Western blotting. Hemorrhagic shock and resuscitation induced the apoptosis in 2LR+SB at 2h and intestinal damage in 2LR+SB at 6h compared to other groups significantly (p<0.01) Apoptosis index of HS+SB at 2h group was significantly reduced compared to 2LR+SB at 2h (p<0.01) and also intestinal damage of HS+SB at 6h group was signiflc
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antly reduced compared to 2LR+SB at 6h (p<0.01). Activation of caspase-3 of HS+SB at 2h group was reduced compared to 2LR+SB at 2h group. On the contrary HSP 70, HSP 40 expression in HS+SB at 2h were higher than 2LR+SB at 2h.
(Liver, Thymus, Spleen) Apoptosis of liver, thymus and spleen were also reduced in HS+SB at 2h compared to 2LR+SB at 2h (p<0.05). FAS and INK in HS+SB at 2h were slightly reduced than 2LR+SB at 2h.
Conclusions : Hypertonic saline resuscitation reduced the apoptosis and intestinal damage after hemorrhagic shock and resuscitation. Thus, the effect of hypertonic saline resuscitation toward apoptosis may have important role in hemorrhagic shock and resuscitation. HS resuscitation may interfere with caspase-3 activation in the small intestine. HS resuscitation may prevent the loss of HSP 70 and HSP 40, which might be involved in the beneficial effect for HS in the small intestine. FAS and INK may be involved in the apoptosis of the liver after hemorrhagic shock and resuscitation. Less
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Research Products
(4 results)
