| Objective: To observe the effects of indole-3-carbinol (I3C) of different dosage on neointimal hyperplasia in rat carotid arteries after balloon dilation for evaluating the possibility of I3C on the prevention and treatment of restenosis after PCI. Methods: Thirty-five male SD rats( weighting 300±50g) were randomly divided into single balloon dilation group(control group, n=5) and balloon dilation followed by I3C therapy group(therapeutic group, n=30). The therapeutic group was subdivided into six sub-group (n=5). After balloon dilation, I3C with a dosage of 12.5mg/d, 25mg/d, 50mg/d were applied to the rats and each dosage were given 4day or 7day respectively. The animals were sacrificed and the carotid arteries were removed two weeks later .The carotid arteries were examined with HE staining, elastic fiber staining and neointimal thickness (H), neointimal area(NIA) , media area (MA), internal elastic membrane(IEM) cross section area , external elastic membrane(EEM) cross section area were measured by computer image analysis system, then the neointimal/media area ratio(NIA/MA), lumen stenosis index(NIA/IEM) were calculated.The immunohistochemical SABC technique and TUNEL method were used to further study the PCNA express and cell apoptosis . Results: 1. Pathomorphometrical analysis: Different degree of vascular smooth muscle cell proliferation were observed in all groups two weeks after balloon dilation,it was most evident in the control group. The neointimal thickness,neointimal area ,NIA/MA and lumen stenosis index in low dosage therapeutic group(12.5mg/d,4d) had a tendency to decreasing ,but there were no statistical significance compared with the control group (P>0.05). The neointimal thickness(44.091±6.206, 33.336±6.651, 31.085±10.644, 26.994±5.251, 12.451±4.593 vs 92.455±39.092) and lumen stenosis index(0.353±0.066, 0.321±0.094, 0.306±0.118, 0.257±0.058, 0.120±0.034 vs 0.605±0.192) in the other therapeutic groups were significant lower than that of the control group(P>0.05). 2.PCNA positive ratio analysis: Excepting the 12.5mg/d,4d group{(53.0±3.5)%v(s55.6±1.9)%,P>0.05}, the percentages of PCNA positive cells in the therapeutic groups was significant lower than that of the control group (37.9±3.9)%, (35.9±1.4)%, (34.0±1.9)%, (27.6±1.7)%, (21.5±1.8)% vs (55.6±1.9)%,there were obvious statistical significance compared with the control group. 3.TUNEL%:Two weeks after balloon dilation,the ratio of positive cells marked by TUNEL in the 12.5mg/d,4d group was(24.6±1.9) % , it had a tendency to increasing compared with the control group(23.4±1.6)%,but there was no statistical difference between them(P>0.05).In the other therapeutic groups, TUNEL% was obviously higher than that of the control group. Conclusion: I3C produced a significant inhibition of neointimal hyperplasia in rats carotid arteries after balloon dilation, this inhibition effect had a obviously dosage-dependent relationship and may partly be related to I3C interfering cell-cycle, inhibiting the proliferation of VSMCs and promoting the apoptosis of cells. These results demonstrate that taking I3C orally can inhibit neointimal hyperplasia and VSMCs proliferation in vivo and has a potential therapeutic benefit in the prevention and treatmentof restenosis after PCI.
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