| Stroke is a cardiovascular disease. It affects the blood vessels that supply blood to the brain. It is the international second leading cause of death. At present, stroke attacked 1.5 million patients every year in China. In 6 million survival stroke patients, 75% lost their labor ability, and 40% were even disabled severely. There are different types of strokes, but regardless of type, surviving a stroke can have a devastating impact, not only on the survivors, but on everyone who cares about them. The direct and indirect economy losses are millions every year. Therefore, stroke therapy and stroke prevention become a very significant project, and draw more and more attention of the international medical workers. It is necessary to found a new strategy for stroke therapy and prevention by thoroughly probing into its pathogenesis.Hypertension is believed an important risk factor for stroke. 78% of the stroke patients had hypertension. Cerebral vessel may rupture and bleed when elasticity of cerebral vessels weakened by lasting hypertension, or when blood pressure increased sharply in some occasions. A high mortality rate reaches 40% without timely therapy.However, we noticed that two hypertension animal models, spontaneous hypertensive rats (SHR) and Stroke-Prone Spontaneously hypertensive rats (SHR-SP) have different time of onset and incidence of stroke. In SHR, hypertension formed at age of 16w with SBP>21.28kPa, but incidence of stroke was less than 10%. However, stroke attacks SHR-SP at age of 12w on average with an incidence of more than 90%. Great differences in stroke incidence in same hypertension setting suggest that some other factors such as changes of cerebral vessel morphology or function may be involved in the pathogenesis of stroke. Numerous data indicated association between location of spontaneous cerebral hemorrhage and intracranial micro-aneurysms. Micro-aneurysms may occur when hypertension lasts. Elasticity becomes weak, thus once blood pressure raised sharply, rupture and hemorrhage occur in micro-aneurysms. Arterial baroreflex (ABR), is the most important self-regulation for blood pressure stability. Dysfunction of ABR was believed participating in several cardiovascular diseases. Our previous study indicated ABR also involves in pathogenesis of stroke.The first part in this study investigated difference of intracranial micro-aneurysms between SHR-SP and SHR. Relationship between micro-aneurysms and blood pressure and ABR functions were evaluated. Furthermore, we investigated difference between SHR-SP and SHR at protein level. Proteins were separated by two-dimensional fluorescent differential gel electrophoresis and differential proteins were identified by tandem mass spectrum. Analysis of these differential proteins may help us found biochemical markers in stroke differences between SHR-SP and SHR.Methods:1. Groups: SHR at age of 28w, male 14, female 11; SHR-SP at age of 28w, male 13, female 13.2. The neurologic impairment was evaluated by Zea Longa.3. Haemodynamics, including blood pressure were recorded and baroreflex sensitivity (BRS) was determined at freely moving state.4. Micro-aneurysms: intracranial micro-aneurysms were identified in pathological sections.5. Proteome techniques: two-dimensional fluorescent differential gel electrophoresis and mass spectrum.Results:1. Incidence of stroke: In 28w SHR, no stroke occur, Zea Longa scored 0. In SHR-SP, 9 of 26 had stroke, significant differences in stroke incidence compared to SHR group (34.62% vs 0, P<0.001), and in Zea Longa score (0.5±0.81 vs 0, P<0.001).2. Micro-aneurysms: No micro-aneurysms was detected in SHR brain slices, however in SHR-SP group, numbers of aneurysms were 2.962±1.509, significantly different from SHR group (P<0.001).3. Relationship between blood pressure and aneurysms: Positive association was found between levels of blood pressure and numbers of aneurysms (r=0.6006, P<0.01).4. Relationship between BRS and aneurysms: In SHR-SP group, BRS was 0.3266±0.122ms/mmHg, significantly lower than that of SHR group (0.5060±0.148ms/mmHg, P<0.001). In SHR-SP, a close negative relation was detected between BRS and numbers of aneurysms (r=0.5441, P<0.01).5. Proteome study: 44 proteins of total 2000 found were differential expressed, 19 of them were highly expressed, 25 of them were lowly expressed in SHR-SP. Preliminary identification of 21 differential expressed proteins of the 44 showed them focus on metabolic enzymes, oxidative stress related proteins and signal transduction molecules.Conclusions: 1. In SHR-SP, numbers of cerebral aneurysms increased dramatically than in SHR.2. Numbers of aneurysms was positive related to blood pressure and negative related to BRS.3. Difference in brain proteins expression exist. Most of them were metabolic enzyme and signal transduction molecules. |
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