Inhibitory Effects Of Icarisid â…¡ On Intimal Hyperplasia In Rat Carotid Arteries Induced By Balloon Injury

Objective: To observe the effects of Icarisid II(Ics II) on vascular intimal hyperplasia in balloon-injured carotid artery of rats and explore the mechanisms.Methods: Twelve rats were randomly selected sham and Sham+Ics II-H(20mg·kg-1)operatio(n=6). After the balloon- injured carotid artery of rats model was established, the survival rats were randomly divided into four groups(n=6): model, Ics II-L, Ics II-M and Ics II-H groups. Ics II-L, Ics II-M and Ics II-H, Sham+Ics II-H groups were offered to Ics(5, 10, 20mg/kg/d) for 14 days. The same volume distilled water was administered in sham group and model group for 14 days. Twenty four hour after the last dose, the neointimal hyperplasia level was observed in the injured side of the vessel with H.E. staining. The neointimal area(NIA) and intimal area / medial area(NIA / MA) were calculated. The apoptosis in carotid artery of balloon-injured carotid artery rats by TUNEL. The content of NO, e NOS, c GMP in rat serum was examined by ELISA. The m RNA expression level of PCNA、NF-κB、e NOS、ERK1、ERK2、c-myc in vascular wall was examined by real-time PCR. The protein expression of PCNA, p-NF-κB(p65), TGF-β1, p-Smad2, p-Smad3, Caspase3, Bax, Bcl-2, Ras, p-ERK1/2 in vascular wall were examined by immunohistochemistry method.Results: Compared with the sham and sham+Ics II-H groups, the lumen area was reduced, and the NIA and NIA/MA were increased in model group(P<0.01). The content of NO, e NOS and c GMP were reduced(P<0.01). The m RNA levels of PCNA, NF-κB, ERK1, ERK2, c-myc and the positive expression of PCNA, p-NF-κB(p65), TGF-β1, p-Smad2, p-Smad3, Caspase3, Bax, Bcl-2, Ras, p-ERK1/2 protein were increased(P<0.05 or P<0.01), the m RNA levels of e NOS were reduced(P<0.01). Ics II could significantly decrease the elevated NIA, NIA/MA ratio(P<0.05 or P<0.01), it was found that the content of NO, e NOS, c GMP and the m RNA expression of e NOS and protein expression of Caspase3, Bax were up-regulated in Ics II-M, Ics II-H groups(P <0.05 or P < 0.01), and the m RNA expression of PCNA, NF-κB, ERK1, ERK2, c-myc and protein expression of PCNA, p-NF-κB(p65), TGF-β1, p-Smad2,p-Smad3, Bcl-2, Ras, p-ERK1/2 were down-regulated in Ics II-M, Ics II-H groups(P < 0.05 or P < 0.01).Conclusion: Icarisid II can significantly attenuate the intimal hyperplasia in rat carotid arteries induced by balloon-injury, which may be related to these possible mechanisms:(1) Ics II can suppress intimal hyperplasia by suppression NF-κB.(2) Ics II can promote VSMC apoptosis by up-regulated of Caspase3, Bax and down-regulated of Bcl-2.(3) Ics II can suppress intimal hyperplasia by promote the formation of NO, e NOS, c GMP.(4) Ics II can suppress VSMC proliferation by down-regulated of TGF-β/Smads pathways.(6) Ics II can suppresss the signal pathway of Ras-ERK1/2.