| Objectives:Intracranial aneurysm(IA) is one of the most common cerebrovascular diseases with abnormal bulging of intracranial vascular wall, and its incidence rate rages from 0.2% to 10% [1]. Once intracranial aneurysm ruptures, the mortality rate will be 30% to 60%. Therefore, intracranial aneurysm is a disease of significant human health threat. Attempt of exposition and exploration of the pathological mechanism behind intracranial aneurysm's formation and development in order to find new prevention and treatment method of intracranial aneurysms has become hotspot in the field of intracranial aneurysms. Currently intracranial aneurysm formation mechanism is not fully unfold, studies have shown that local hemodynamic change is the key factor in intracranial aneurysm formation. In addition, the local inflammation in vessel wall contributes to the development of intracranial aneurysm. There are varieties of inflammatory pathways involved in the formation and development of intracranial aneurysms, and NF-?B-related inflammatory pathways play an important role in the occurrence of intracranial aneurysm development. In this study, we used bilateral carotid artery ligation method to produce rabbit basilar artery aneurysm formation model. And we give these animals DG via ear vein injection to observe the interventions effect of DG during the formation of rabbit basilar artery aneurysm model.Method: The experimental new zealand white rabbits were randomly divided into four groups, control group(group A), non-intervention group(group B), intervention group(group C) and normal saline group(group D). The control group received bilateral common carotid artery exposure. Rabbits in the rest groups were operated with bilateral common carotid artery ligation to produce basilar artery bifurcation aneurysm model. In the first 7 days after modeling, group Breceived no treated, while rabbits in group C were given diammonium glycyrrhizinate(20mg/kg·day-1) via ear vein injection. Rabbits in group D were given same dose of normal saline in the same way. Before modeling and in the seventh day after modeling, blood flow rate and vascular morphology were acquired using transcranial doppler sonograph(TCD)and MRA respectively. Then rabbits in all groups were killed with an excess anesthesia in 7th day after ligation. Thebasilar terminusand tissue from brain stem nearby were removed to produce paraffin sections after dehydration fixed. EVG staining was preformed to measure internal elastic lamina loss in the basilar terminus, while masson staining was preformed to measure the thinning condition of media of basilar terminus. The condition of NF-?B and MMP-9 were measured via immunohistochemical staining while ?-SMA via immunofluorescence staining. Enzyme-linked immunosorbent assay(ELISA) was used to detect TNF-? and MCP-1 expression in the basilar terminus.Result: Wall shear stress change inbasilar terminus: Before modeling:(32.29±12,27)Pa, after modeling(104.80±28.15)Pa. Compared with the WSS before modeling, WSS after modeling had statistically significant difference(p<0.05).Internal elastic lamina loss and thinning condition of media in rabbits' basilar terminus. Internal elastic lamina loss: group B:(171.0±50.09)?m, group C:(121.4±28.57) ?m, group D:(186.1±58.21)?m. Group C compared with group B had statistically significant difference(p<0.05), group C compared with group D had statistically significant difference(p<0.01). Thinning condition of media: group B:(144.3±51.64)?m, group C:(91.66±25.65) ?m, group D:(162.0±60.75)?m. Group C compared with group B had statistically significant difference(p<0.05), group C compared with group D had statistically significant difference(p<0.01).NF-?B and MMP-9 expression in rabbits' basilar terminus: NF-?B(%): group A:(10.47±1.92), group B:(20.20±3.16), group C:(14.66±3.65), group D:(21.71±6.52). group C VS group B had statistically significant difference(p<0.05), group C VS group D had statistically significant difference(p<0.01). MMP-9 expression(%): group A:(18.20±3.29), group B:(29.42±6.56), group C:(22.62±4.19), group D:(31.95±7.26). Group C VS group B had statistically significant difference(p<0.05), group C VS group D had statistically significant difference(p<0.01).?-SMA expression in rabbits' basilar terminus: ?-SMA expression(%): group A:(80.03±3.44), group B:(60.42±12.00), group C:(70.67±4.97), group D:(57.25±9.07). group C compared with group B had statistically difference(p<0.05), group C compared with group D had statistically significant difference(p<0.01).TNF-? and MCP-1 expression: TNF-?: group A:(23.34±4.85)ng/L, group B:(56.84±9.78)ng/L, group C:(44.36±5.25)ng/L, group D:(58.53±9.46)ng/L. Group C compared with group B and Group D had statistically difference respectively(p<0.05). MCP-1: group A:(63.60±7.95)ng/L, group B:(99.36±11.58)ng/L, group C:(80.68±5.69)ng/L, group D:(93.98±10.51)ng/L. Group C compared with group B and D had statistically difference respectively(p<0.05).Conclusions: Blood flow rate and WSSinbasilar terminus increased obviously after modeling.Destructive remodeling such as IEL loss thinning media and outward bulge which was resulted by the change of hemodynamic changes appeard in basilar terminus.NF-?B related pathway involved in the formation of intracranialaneurysm.NF-?B, MCP-1, TNF-? and MMP-9isupregulationwhile?-SMAisdownregulation.DG surpresses the expression of NF-?B, MCP-1, MMP-9andTNF-?, and maintain the expression of ?-SMA. DG can intervent the formation of IA. |
PDF Full Text Request