Expression And Correlation Of NF-Kappa B And Vascular Endothelial Growth Factor In Intracranial Aneurysm And Vascular Remodeling

Objective:1.To study the pathology and ultramicrostructure of human intracranial aneurysm.2.To examine the expression of NF-kappa B(NF-κB)and vascular endothelial growth factor (VEGF)in human intracranial aneurysm and evaluate their importance in the pathogenesis human intracranial aneurysm.3.To evaluate the relationship between NF-κB and VEGF as well as their effect with the remodeling of the vascular wall.Methods:Experimental group:26 samples of intracranial aneurysms were obtained by operation during Feb 2006 to Aug 2007 in the second hospital of Shandong University.Of all the samples,15 males,11 females,aged from 22 to 65 years old and averaged 49.There were 7 cases which diameter smaller than 0.5cm,15 cases between 0.5-1.5cm and 4 cases bigger than 1.5cm.Control group:10 normal cerebral vessels were obtained by operation from brain trauma cases.All samples were examined using HE and immunohistechemistry stain technique.All the stained sections were observed under the microscope recording the positive site and intensity,and histopathology was taken to observe the arteriosclerosis of the vascular wall.RT-PCR was adopted to examine the mRNA of NF-κB and VEGF in intracranial aneurysm.Results:(1)H&E stainingIn aneurysm group,the normal three-layer structure had lost in all intracranial saccular aneurysm walls,the fundamental histopathological changes were inury, denaturalization and repair.Most aneurysms specimens showed structure changes, including injury of endothelial cell,disrupture or disappearance of the intemal elastic layer,scarce of contractile fiber cells.The number of smooth muscle cell become less, the left SMC swelled and become denaturalization,the middle layer was filled with fibre tissue;the outer layer turned thinner,most was fibre tissue,no outer elastic layer.In all layers of aneurysm were coated with more or less inflammation cells,the regional necrosis and different stage of atherosclerosis could be detected in relative large aneurysms,but were rare in relatively small ones.(2)Immunohistechemistry stain:The positive expression of NF-κB in all 26 samples was 88.5%(23/26)with expression every layer in the wall of aneurysm.NF-κB was mainly expressed in the inner and middle layer of aneurysm and endothelial cell,smooth muscle cell,mechanocyte and inflammatory cell.Positive expression of NF-κB in the wall of intracranial aneurysm shows a claybank staining of the nucleus.The expression of NF-κB in the control vessel was 20%(2/10)and the only expression place was cytolymph(P＜0.01).The positive expression of VEGF in all 26 samples was 80.8%(21/26)with expression every layer in the wall of aneurysm.VEGF was mainly expressed in the inner and middle layer of aneurysm and endothelial cell,smooth muscle cell,mechanocyte and inflammatory cell.Positive expression of NF-κB in the wall of intracranial aneurysm shows a claybank staining of the nucleus.The expression of VEGF in the control vessel was 20%(2/10)and the only expression place was cytolymph(P＜0.01).The expression of NF-κB and VEGF were positively correlated in aneurysms(r_s=0.690).(3)RT-PCR:RT-PCR shows a positive expression both NF-κB and VEGF.Conclusion:Rupture or disspearence of internal elastic layer,soakage of inflammation cell, different stage of atherosclerosis,apoptosis of SMC and changes of ECM,and so on are the pathological and morphological base of the occurrence and development of ISA.NF-κB is activated during the progression of ISA and play a very important mediation role in the inflammatory reaction and remolding of the vessel wall. VEGF is highly expressed in the wall of ISA and mainly in it's resultant field.The thickness of the wall of ISA is different.The wall becomes thin when the VEGF and NF-κB express raised up while becomes thick where the two factors expressed slowed.The remolding of the ISA is mainly positive and dilatancy.The change of arteriosclerosis is normally before middle time.The size of ISA is relative with the age of patients.The local hemodynamics maybe plays an important role in the active expression of VEGF and NF-κB.The expression of NF-κB and VEGF were positively correlated in aneurysms and play a very important cooperate fact in the progress of ISA and arteriosclerosis.