Effect Of All-trans Retinoic Acid On The Expression Of Serum IL-1β And The Expression Of NF-κB And P-selectin In Atheroscierotic Plaques In Rabbits

Objective To observe the influence of all-trans retinoic acid(ATRA) on intimal proliferation and the expression of NF-κB and P-selectin in atherosclerotic plaques and serum IL-1βlevel in rabbits.Methods 54 New Zealand rabbits were randomly divided into 9 groups: sham-operation groups(A,B,C), control groups(A,B,C), treatment groups(A,B,C). There were 6 rabbits in each group. The sham-operation groups were fed with conventional chow, and underwent surgery without endothelium injury; The control groups were fed with high cholesterol chow and subjected to carotid endothelial injury by air desiccation after 2 weeks; The treatment groups were administered ATRA daily by gavage, and other measures were same with the control groups. The rabbits in the B groups were subjected to collecting blood before and after 1,4,7 and 14 days since surgery respectively. ELISA were used to detect the serum IL-1βlevel. The rabbits in the A groups, B groups and C groups were sacrificed respectively after 7.14 and 28 days since surgery. The carotid artery segments were harvested for histomorphometry observation and determination, and immunohistochemistry were used to detect the expression of NF-κB and P-selectin.Results①The thickening of intima was not found in the sham-operation groups and the expression of NF-κB and P-selectin was microscale.②In the control groups, the thickening of intima was found in carotid artery after 7 days since surgery, and severe thickening of intima and atherosclerotic plaques were found after 14,28 days. The expression of NF-κB and P-selectin of control groups were significantly detected.③In the treatment groups, the intimal area, intimal/medial area ratio and maximum plague thickness of the artery after 14.28 days since surgery were lower than the control groups(all P<0.05), and the expression of NF-κB and P-selectin were lower too(all P<0.05).④In control groups, the serum IL-1βlevel had increased apparently since 4 days after surgery. The condition would also be found in the treatment groups, but the IL-1βlevel was more lower than that of the rabbits in control groups. Conclusion The results show that ATRA can inhibit neointimal formation after carotid endothelial injury in rabbits. and the possible mechanism is that ATRA inhibits the acivatior and expression of NF-κB and then decreases the expression of P-seiectin and IL-1βwhich is regulated by NF-κB and ultimately inhibits the inflammation.