1998 Fiscal Year Final Research Report Summary
Moduration of the molecular chaperone activity to increase the safety of extended liver surgery in the damaged liver patients -- challenge by the induction of stress response and heat shock gene transfection --
| Project/Area Number |
09307026
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YAMAOKA Yoshio Kyoto university, Dep. Gastroenterol. Surg, Professor, 医学研究科, 教授 (90089102)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Yuzo Kyoto university, Dep. Gastroenterol. Surg, Instructor, 医学研究科, 助手 (70281730)
IKAI Iwao Kyoto university, Dep. Gastroenterol. Surg, Lecturer, 医学研究科, 講師 (60263084)
SHIMAHARA Yasuyuki Kyoto university, Dep. Gastroenterol. Surg, Associate Professor, 医学研究科, 助教授 (30196498)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Extended liver Surgery / Molecular chaperone / Heat shock protein / Ischemia-reperfusion Injury / Ischemic tolerance / Preconditioning / Hyperthermia / Damaged liver |
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| Research Abstract |
1. Evaluation of maximally resectable volume of the liver by Non-touch isolation method
Animal survival for more than 5 days was constantly obtained in the left trisegmentectomy with this technique as long as ischemic period was limited within 90 minutes and hepatic temperature during ischemia was kept at about 20℃. Cooling of the liver is not sufficient in in situ perfusion in comparison to the ex-situ operation because the liver is maintained in the corpus without cutting the hepatic hilum. However, this technique has big advantages in simplifying surgical technique and shortening operation time because neither the reconstruction of hepatic artery or bile duct is necessary. As a result, there was no difference in the resectable hepatic volume between this technique and conventional hepatic resection.
2. Investigation on the liver protection by modurating molecular chaperon activity
1)Analysis on the changes in intracellular milieu by heat shock preconditioning
We have already reported th
… More
at HSP72 was produced by heat shock preconditioning and this protein was involved in the acquisition of stress tolerance. Here, we found that the activation of NFκ-β and the production of TNF-α were suppressed by heat shock preconditioning. Further investigation is needed to know the relationship between these findings and heat shock proteins.
2)Acquisition of stress tolerance by heat shock gene transfectlon to the liver
We established the method to transfect the myoglobin and matrix metalloprotease gene into hepatocytes using adenovirus. We are now studying how to transfect HSP 72 in hepatocytes by this method.
3)Induction of stress response of the liver
In addition to the HSP72 induction, inhibition of TNF-α production was involved in the stress response to the treatment by Doxorubicin. We also found that repeated heat shock preconditioning increased the expression of HSP72 protein and ischemic tolerance. Moreover, we revealed that the pretreatment of geranyl-geranyl-acetone (GGA) intensified stress response and that 5-minute heat shock with GGA pretreatment produced ischemic tolerance to the same extent as 15-minute heat shock without pretreatment. Less
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