The Study On The Pathogenesis Of The Growth Of The Experimental Saccular Aneurysms In Rats

The study on the pathogenesis of the growth of the experimental saccular aneurysms in ratsObjective To study the possible pathophysiological mechanisms of the growth of the experimental saccular aneurysms in rats.Methods (1) Through microsurgical direct destruction of the arterial intima and internal elastic lamina at the bifurcation of the carotid artery in 30 rats,saccular aneurysms can be induced immediately, and the contralateral carotid arterys were ligated in half of them. All of the rats were raised for 4-5months.(2) The expressions of Type III collagen on the walls of the normal carotid arteries and the saccular aneurysms were determined by the immunohistochemistry. (3) The expressions of PDGF-B on the walls of the normal carotid arteries and the saccular aneurysms were examined by the immunohistochemistry and in situ hybridization. (4) The primary culture of smooth muscle cells of rat aorta was estabilished and the effects of PDGF-B and IL-1 a on the expressions of MMP-1,2,9 and TIMP-1 were detected by the immunohistochemistry and RT-PCR.Results (1) Saccular aneurysm can be induced immediately by destroying the intima and internal elastic lamina at the bifurcation of the carotid artery in rats.(2) Saccular aneurysms grow significantly due to by the hemodynamic stress in4-5 months (P<0.01) , and much bigger after the ligation of the contralateral carotid artery which enhances the hemodynamic stress(P<0.01). (3) There is Type III collagen expression on the media of the normal carotid artery in rats, but its expression decreases on the aneurysmal walls and further reduced with the growth of the saccular aneurysms.(4) There is no PDGF-B expression on the wall of the normal carotid artery in rats,but it appears on the aneurysmal walls and more distinctly with the growth of the saccular aneurysms (P<0.05) . (5) The aorta smooth muscle cells can secrete MMP-2 and TIMP-1 without PDGF-B and IL-1 a , and there are no significant effects of PDGF-B and IL-1 a on the expression of MMP-2 and TIMP-1. (6) The aorta smooth muscle cells cannot secrete MMP-1 and MMP-9. Neither PDGF-B nor IL-1 a alone induces the expression of MMP-1 and MMP-9 in the aorta smooth muscle cells ,however,PDGF-B can induce their expressions synergistically with IL-1 a .Conclusion There is PDGF-B expression on the wall of the saccular aneurysm, PDGF-B is able to induce the expression of MMP-1 and MMP-9 synergistically with IL-1 a for degradation of the extracellular matrix, especially Type III collagen, on the aneurysmal wall, this may be one of the important mechanisms on the growth of the intracranial saccualr aneurysm.