| Cerebral aneurysm is one of the most severe forms of cerebrovascular diseases, its rupture is the main cause of death and neurological deficit. Although, in recent years, remarkable advances have been achieved in cerebral aneurysm therapy of Microneurosurgery and Interventional Neuroradiology, it is also very dangerous to treat the aneurysms. So in order to reduce the morbidity and mortality rates followed the rupture of cerebral aneurysm, it is very important to enhance the study on the molecular mechanism of cerebral aneurysm formation and seek the therapeutic innovation to prevent the cerebral aneurysm from growth.Early investigation hypothesized that aneurysm formation was the result of the degradation of intimal pad, the main component of the artery wall, as cerebral blood vessels passively responded to exaggerated homodynamic force for a long time. Latest studies have demonstrated that the imbalance of extracellular matrix metabolism is associated with the degradation of intimal pad. Matrix metalloproteinases (MMPs) are a family of Zn2+ -dependent proteinases that degrade components compounds of the extracellular matrix (ECM). These enzymes play a pivotal role in turnover and remodeling of the ECM during organism growth and development and the pathological destruction of tissues in diseases. Increased MMP-2,MMP-9 and tissue inhibitors of metalloproteinases(TIMPs) levels have close relationship with the cerebral aneurysm formation. Nuclear factor-κB(NF-κB)is a transcription factor, which can mediate the expression of many cytokines and participate in a number of pathological processes includinginflammation, cell proliferation and apoptosis. Sequence analysis has revealed that a specific functional NF-κB binding site is present in the proximal stimulatory region of the MMPs promoter and deletion of this site can reduce upregulation of MMPs gene. At present, Little is known about the expression changes of the NF-κB and MMPs and the relationship between them in the process of aneurysm formation. So, with the help of the model of cerebral aneurysm induced by renal hypertension in rats, we examined the expression of NF-κB and MMPs at different time points in the process of aneurysm formation at the level of gene expression and protein activity, furthermore, in order to find the drugs which can prevent or suppress the cerebral aneurysm development, we treated the rat with the MMPs inhibitor-doxycycline and NF-κB inhibitor-triptolide and evaluated the ability of two in preventing the cerebral aneurysm form formation. There are five parts in this study.1 Pathogenetic Study of Cerebral Aneurysm Induced by Renal Hypertension in RatsThe purpose of this study is using light and electron microscopy to investigate the relationship between the early histological changes of cerebral arteries and the cerebral aneurysmal formation induced by renal hypertension in rats according to the modified Hashimoto's method. In this study, fifty male Sprague-Dawley rats weighing 150 to 200g were divided into two groups: experimental group (40 rats) and control group (10 rats). All animals were anesthetized by intraperitoneal injection of sodium pentobarbital (40mg/kg). The posterior branches of bilateral renal arteries were coagulated with a bipolar coagulator under surgical microscope in animals of experimental group. One week later, the left common carotid artery of the animal was coagulated and cut according to the same procedure. Subsequently, the animals were watered by 1% saline solution in order to enhance the hypertension. Sham-operations were done in control animals.Tail systolic blood pressure was measured by an electronic blood pressure meter in all rats just before the operation, 1, 3 days, 1, 2, 3 weeks, 1, 2 ,3, 4 months after the operation. Four months later, the animals were transcardially perfused with 300ml of physiological saline, followed by 400ml of 4% paraformaldehyde in 0.1M phosphate buffer(pH 7.4, 4℃). The brains were removed and postfixed in 2.5% glutaraldehyde in 0.1M p... |
