[Experimental study on rho-kinase inhibitor by intravenous injection inhibiting intimal hyperplasia in vein grafts].
OBJECTIVE
To investigate the effects of Rho-kinase inhibitor--fasudil hydrochloride hydrate on vein graft intimal hyperplasia in vivo.


METHODS
Twenty-four healthy rabbits (2.3-2.5 kg) were randomly divided into two groups (n=12). Fasudil hydrochloride hydrate (experimental group) and normal sodium (control group) were given 3 days before operation with 30 mg/kg by intravenous injection everyday and continued until the end of the experiment. After a longitudinal incision, the femoral vein and the femoral artery were exposed about 3 cm. An approximately 2.5 cm segment of the famoral vein was harvested for the reversed-vein graft. The femoral artery was removed 1 cm segment and replaced by the harvested femoral vein. At 2 and 4 weeks after operation, the grafts were stained with HE to observe the thickness of the intima. Furthermore, the proliferating cell nuclear antigen (PCNA) and transmission electron microscope was used to study the proliferation of smooth muscle cell. In situ apoptosis was detected by TUNEL assay.


RESULTS
All rabbits survived till the end of the experiment. The color Doppler imaging examination showed that all grafts were patency. At 2 and 4 weeks after the operation, HE staining showed that the intimal hyperplasia were obvious in the two groups. There were lots of cells in the intima, and more fusiform smooth muscle cells in the media. At 2 and 4 weeks, the intimal thickness were (30.33 +/- 3.23) microm and (43.11 +/- 4.92) microm in experimental group and were (44.83 +/- 3.53) microm and (66.16 +/- 8.45) microm in control group. The rates of PCNA positive cell were 14.28% +/- 2.76% and 7.61% +/- 1.06% in experimental group and were 20.08% +/- 3.56% and 8.73% +/- 1.35% in control group. The rates of TUNEL positive cell were 3.55% +/- 0.36% and 1.22% +/- 0.18% in experimental group and were 1.11% +/- 0.31% and 0.55% +/- 0.11% in control group. There were significant differences (P < 0.05) between the two groups at 2 weeks or 4 weeks, between 2 weeks and 4 weeks within group.


CONCLUSIONS
Intravenous injection of fasudil hydrochloride hydrate is an effective method for prevention of vein graft intimal hyperplasia of rabbit.
Zheng
Zhanle
Z
Department of Orthopaedics Trauma Center, the Third Hospital of Hebei Medical University, Shijiazhuang Hebei, 050051, PR China.
Pan
Jinshe
J
Ma
Lijie
L
Yu
Xian
X
Guo
Mingke
M
Yao
Shuangquan
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D005260:Female; D006085:Graft Survival; D006965:Hyperplasia; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D014680:Veins / Q000637:transplantation*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil