| Nowadays, cerebrovascular disease is still one of the three major fatal disease which is a hazard to human health.With the arrival of global aging,the incidence of cerebral infarction is as expected continue to rise over the next 20 years. Its high incidence,high morbidity, high mortality, and high recurrence rate, and gradually young characteristics, has caused serious social and family burden. So, the research of treatment on stroke is still an important task for the domestic and foreign scholar and scientists.Evidence based medicine has proved that recombinant tissue plasminogen(rt-PA) is the only effective drug for the clinical treatment of acute cerebral infarction within the effective time window. However, due to the restriction of short time window of thrombolytic and hemorrhagic after thrombolytic therapy, only 3%-8.5% patients of stroke can benefit from it.How to give paitients with acute cerebral infarction more effective treatment on the basis of Western medicine treatment is always a hard work for us. At this time, Chinese medicine and treatment brought us a promising future. Chinese medicine is a compound which containing a variety of ingredients, after reasonable compatibility of various herbs, Just have such a multi-mechanism, multi-target therapeutic advantages. Previous, the research of cerebral ischemia thearpy mainly focus on the neuroprotective aspect, because of the limited mechanism, it has receive little return. Each cell can surivival depends on the interaction and signal transduction of them after ischemia. Therefore only neuroprotection or vascular protection is inadequate to improve the defects. The study of traditional Chinese medcine Kangnaoye can be though the protection of nerves, vessels andother aspects to release the cerebral ischemia reperfusion injure, has great practical significance in guiding clinical practice.The mechanisms of cerebral reperfusion injure is complex, the injure itself can stimulate the brain endocrine various neurotrophic factors, some of neurotrophic factors with a double protection nerves, blood vessels, such as vascular endothelial growth factor(VEGF), brain-drived neurotrophic factor(BDNF). Meanwhile, cerebral ischemia induce the release of inflammatory cytokines, destroy the integrity of blood-brain barrier,causing cerebral edema and hemorrhagic transformation, further aggravating the clinical manifestations of neurological deficit. Wherein, the matrix metalloproteinase involved in the inflammatory injury, and play a negative impact on other aspects of maintaining the blood-brain barrier function.The experiment through establish cerebral ischemia and repefusion model in rat, To observe the effect of Kangnaoye pretreatment on nerve function, Infarct areas and morphological at different time points in SD rats after cerebral ischemia and reperfusion. Observe the expression of vascular endothelial growth factor(VEGF), brain derived neurotrophic factor(BDN F), matrix metalloproteinase-9(MMP-9), and extracellular signal-regulated kinase(ERK1/2) in rats with cerebral ischemia-reperfusion injury, and the effect of Kangnaoye on the results. Explore the protective mechanisms of Kangnaoye against the injury of cerebral ischemia-reperfusion.In this study, Male Spraque-Dawley rats were randomly divided into:normal group(Normol n=36), Sham operation group(Sham–operated, n=36),cerebral ischemia-reperfusion group(I/R, n=36), Kangnaoye high dose group(KNY H, 28.6 g·k-g-1·d-1 n=36), Kangnaoye medium dose group(KNY M, 14.3g·k-g-1·d-1, n=36), Kangnaoye low dose group(KNY L,7.15g·k-g-1·d-1, n=36). Improved Zea Longa method was used to prepare cerebral ischemia-reperfusion model of rats. Reperfusion after ischemia for2 h(rats were sacrificed respectively after reperfusion 6 h, 12 h, 24 h, 72 h,7d). The method of Longa’score was used for neurobehavioral score; TTC stianing method was used for observing the infarct area of rats brain; HE staining tissue sections, observe the pathological changes in brain tissue using optical microscope; Immunohistochemical method and In situ hybridization method was used for observing the expression of VEGF,BDNF, MMP-9, p-ERK1/2 in rats brain tissue.Compared with the normol and shamed group, the change of neurobehavior and neurological deficits in the model group was obvious;the area of cerebral infarction was obvious and larger, the neurons’ swelling were very apparent; the expression of VEGF, BDNF, MMP-9, p-ERK1/2 in brain tissue was upregulated, the difference was significant(P<0.05 or P<0.01). Compared with ischemia-reperfusion group, It was found that the neurological scores, infarct size, and the neuronal swelling, interstitial edema pathological change of rats was improved in varying degrees in Kangnaoye High and Middle dose groups, the expression of VEGF, BDNF,p-ERK1/2 in Kangnaoye High, middle groups were upregulated(p<0.01)and the expression of MMP-9 decreased, showing statistically significant( p<0.01). However, there was no significant difference between Kangnaoye low dose group and I/R group(P>0.05).Kangnaoye promote the expression of VEGF, BDNF in brain tissue of focal cerebral ischemia, activates ERK1/2 signaling pathway meanwhile inhibit the expression of MMP-9, decrease the infarct area and neurobehavioral score, thus play a protective role in cerebral ischemia reperfusion injury. |
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