[Administration of sirolimus affects vein graft neointima hyperplasia].
OBJECTIVE
To investigate the effect of Sirolimus on vein graft neointima hyperplasia via oral administration compared with local delivery, and find out an effective and safe way to provide support for clinical application.


METHODS
A rabbit external jugular vein-to-common carotid artery model was established. Twenty-four healthy rabbits were divided into 4 groups at random: blank-control group, F-127 control group, group 3 that received locally applied slow-releasing Sirolimus with F-127, group 4 that received oral Sirolimus (the commercial name Rapamune). The ratio of intima to medium thickness and re-stenosis rate (ratio of lumina to lumina plus intima area) were measured, PCNA positive cells by immunohistochemical staining were detected to indicate the degree of cell proliferation, and apoptosis cells detected by TUNEL.


RESULTS
Compared with blank-control group, neointima hyperplasia was inhibited significantly in group 3 and group 4 [intima thickness were (90.11 +/- 10.99) microm versus (29.38 +/- 10.45) microm, (18.29 +/- 9.03) microm, respectively]. Re-stenosis rate was reduced (lumina area/ total area ratio were 0. 58 +/- 0.11 versus 0.80 +/- 0.16, 0.77 +/- 0.16, respectively). Proliferation of VSMC was inhibited (cell proliferation indexes were 31.03%+/-6.80% versus 20.32% +/- 9.19%, 16.22% +/- 5.85%, respectively) and cell apoptosis level raised (cell apoptosis indexes were 16.27% +/- 6.49% versus 33.39% +/- 7.05%, 33.42% +/- 7.11%, respectively). There was no significant difference between group 3 and group 4.


CONCLUSIONS
Both locally applied slow-releasing Sirolimus and oral Rapamune could inhibit vein graft neointima hyperplasia; Administration via local delivery was preferred for little side-effect on the whole body. This conclusion provides support for clinical application.
Xiao
Feng
F
Department of Cardiac Surgery, Peking University First Hospital, Beijing 100034, China. qing.fan.1@sohu.edu
Zhang
Lu-feng
LF
Shi
Zhi-hui
ZH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017536:Carotid Artery, Common / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D023903:Coronary Restenosis / Q000517:prevention & control; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006965:Hyperplasia / Q000517:prevention & control; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D020287:In Situ Nick-End Labeling; D007601:Jugular Veins / Q000637:transplantation*; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D020123:Sirolimus / Q000008:administration & dosage*; D017539:Tunica Intima / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology
D007166:Immunosuppressive Agents; D018809:Proliferating Cell Nuclear Antigen; D020123:Sirolimus