Correlation of motility and neuronal characteristics in intestinal allograft chronic rejection

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18591422
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Keio University
• Principal Investigator: HOSHINO Ken Keio University, School of Medicine, Assistant Professor (70190197)
• Co-Investigator(Kenkyū-buntansha): MORIKAWA Yasuhide KEIO University, School of Medicine, Professor (90124958) ; WATANABE Toshihiko KEIO University, School of Medicine, Researcher (50306734)
• Project Period (FY): 2006 – 2007
• Keywords: small bowel transplantation / chronic rejection / motility / neuronal cell / interstitial cells of Cajal

Research Abstract

【Aim】The aim of this study was to elucidate correlation between motility and neuronal integrity for chronic rejection after small bowel transplantation in rats.
【Material and Method】
Orthotopic SBTx was performed and recipients were divided following three groups; group 1: Allogenic SBTx from Brown Norway (BN) to Lewis (LEW) was done with FK506 at a dose of 2mg/kg, intramuscularly, day0-5, which is considered as chronic rejection model. group 2: Allogenic SBTx was also done with FK506 at a dose of 2mg/kg i.m., day0-9, which served as long-term functional model. group 3: Syngenic transplant was prepared from BN to BN without FK506. On day 80, three miniature strain gauge force transducers were set on the graft to evaluate motility pattern in vivo. Wholemount of the grafts were applied into cuprolinic blue staining and immunohistochemistry to assess population of neuronal cell and interstitial cells of Cajal (ICC). H-E histological examination of the intestinal grafts was also performed to define the chronic rejection.
【Results】
Histology of the Intestinal Grafts
In group 1, arterial wall thickening as vascular sclerotic findings and thickening in the muscular layer was observed in H-E staining which was fit in the definition of chronic rejection. Whereas the other 2 groups had no finding of rejection.
Motility of the Intestinal Grafts
The parameter of MMC phase III has a characteristic alteration among these groups. The duration and interval of MMC
phase III has a significant difference between group 1 and group 3. (syngenic model vs chronic rejection model
Duration ; 6.2±1.8 (min) vs 5.7±1.7 (min) (p<0.01), Interval ; 19.1±5.3(min) vs 16.7±4.3(min) (p<0.0001))
Labeling-neuronal cells and ICC
We are still under investigation.
[Conclusion] This study provides important characteristics on motility in chronically rejected intestinal allogtafts. The motility parameter including duration and interval of migrating motor complex indicates a key role for diagnosing chronic rejection. We are still under investigation on the alteration of the neuronal condition, but we believe these approaches will reveal the correlation with dysmotility of the grafts.