Expression Change Of Endothelin-1 And Interleukin-6 Gene In Rabbit Basilar Artery In An Experimental Model Of Cerebral Vasospasm After Subarachnoid Hemorrhage

Cerebral vasspasm associated with aneurismal subarachnoid hemorrhage has been recognized for over half a century and remains a major complication of aneurysmal SAH. Delayed cerebral vasospasm leading from cerebral vasospasm is an important cause of mortality and neurological dysfunction. It has been researched for more than half century, but the pathophysiological mechanisms contributing to cerebral vasospasm are still not clear. Such studies seek to identify the mechanisms underlying cerebral vasospasm and to develop effective clinical strategies for improving patient prognosis.Endothelins are among the most potent endogenous vasosactive agents yet identified. Endothelin-1, the most extensively studied of the ET family. The most prominebt action ET-1 exerts is a strong vasoconstriction that is mediated by specific membrane receptor. Several lines of evidence have implicated ETs in the spatic response to SAH. First, hemolysate such as oxyhemoglobin can increase the production and release of ET. Second, ET-1 elicits a potent and prolonged constriction of cerebral vessels. Third, several clinical studies have shown that levels of ETs are elevated in the cerebrospinal fluid of patients after occurs. Finally, experimental studies indicate that ET receptor antagonists attenuate cerebral vasospasm in animal models of SAH. All of thess findings support the concept that ET contributes to arterial narrowing after SAH occurs.Inflammatory reactions are also among the major mechanisms that lead to ischemic injuries of the brain that may occur after SAH. The occurrence of a high concentration of cytokines 4-10 days after ASH coincides with the vasospasm. The increase of IL-6 was demonstrated in patients after SAH, with DINDs as a result of vasospasm.To study the expression change of endothelin-1 and interleukin-6 gene in the basilar artery of rabbit and the effect of endothelin-1 and IL-6 on the development of cerebral vasospasm induced by experimental subarachnoid hemorrhage. Thirty healthy China White Rabbits were randomly divided into saline-control group and experimental group. The experimental group was subdivided into four groups, representing day 3, 5, 7 and 14 after the first blood injection of SAH. The delayed cerebral vasospasm (DCVS) model was established by double injection of autologous blood into the cisterna magna. The expression change of ET-1 and IL-6 mRNA in the basilar artery was analyzed by Real Time RT-PCR. All samples were performed in triplicate, and relative expression of ET-1 and IL-6 were determined by normalizing to GAPDH to calculate a fold change in value.Gene expression was calculated using the comparative delta-delta-Ct method. The expression of ET-1 gene increased on day 5-7 after the first blood injection of SAH compared with control (P < 0.001), and decreased to normal on day 14. The expression of IL-6 gene increased on day 3-5 after the first blood injection of SAH compared with control (P < 0.001), and decreased to normal on day 14. Conclusion The expression level of ET-1 and IL-6 gene in basilar arteries was intimately associated with the degree of cerebral vasospasm, suggesting that ET-1 and IL-6 may play an important role in the DCVS after SAH.