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The Effect Of Kang Nao Ye On The Expression Of VWF、BFGF And PI3K/Akt Signal Transduction Pathway Of Rats With Cerebral Ischemia-reperfusion Injury

Posted on:2015-12-09Degree:MasterType:Thesis
Country:ChinaCandidate:Z J XiaoFull Text:PDF
GTID:2284330467970199Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Cerebrovascular disease (ICVD) is one of the major diseases thatendanger people’s health, which has the characteristics of high morbidity,high mortality, high disability and high recurrence rate. At present, Chinahas entered the aging society, the incidence of ICVD tend to increasegradually. In recent years, a lot of manpower and resources have beeninvested to carry out research on ICVD treatment in domestic and foreign,mainly for neuronal metabolism, microcirculation dysfunction, acidosis,energy depletion, toxic effects of excitatory amino acids, free radicaldamage, inflammatory cytokines damage, oxidative damage and so on, andthe incidence of these injuries can be attributed to the foundation of ICVD:Brain ischemia and hypoxia. So how to achieve early recovery bloodsupply has become the key to the treatment of ICVD. Studies have shownthat the prognosis of stroke patients with high-density cerebrovascular issignificantly better than the low density. Cerebral angiogenesis can improveblood supply to the brain, so as to reduce the neurological deficits as muchas possible. The degree of angiogenesis in the ischemia area is related tothe recovery of neurological function. With the therapeutic angiogenesisproposed, the field of research involves gene therapy, protein therapy, stemcell transplantation and so on, but these treatments are expensive. At thesame time, the safety and efficiency remain to be further evaluated. Thereis still a distance away from clinical application. A large number of studieshave shown that traditional Chinese medicine which has small side effectscan promote angiogenesis has been confirmed. It provides a broad prospectfor the treatment of ICVD. Kangnaoye consists of astragalus membranaceus and salvia miltiorrhiza, puerarin, uncaria, rhizoma ligusticiwallichii, notoginseng powder and so on, which can supplement qi andpromote blood circulation by removing blood stasis, clear heat, calm theliver. Through making cerebral ischemia reperfusion model, thisexperiment can observe the effect of Kangnaoye on the expression of bFGFand the PI3K/Akt signal transduction pathway, thus to explore themechanism of Kangnaoye in ischemic cerebrovascular disease, and providea reliable theoretical basis for clinical application.The animal models of middle cerebral artery occlusion (MCAO) wereestablished by a monofilament method from right internal carotid artery.Rats were given reperfusion by12h,24h,48h,72h,168h respectively afterischemia for2h. The216healthy male SD rats were randomly divided into6groups: Kangnaoye high dose group (KNY H, n=36), Kangnaoyemedium dose group (KNY M, n=36), Kangnaoye low dose group (KNY L,n=36), Nimodipine group (n=36), model group (n=36), sham operatedgroup (n=36). Neurological evaluation was performed after reperfusion, thepathological change was detected by HE staining and the volume change ofcerebral infarction in rats was detected by TTC Staining.Immunohistochemical method was used to investigate the vascularendothelial cell markers: vWF, bFGF and PI3K/Akt, and the expression ofPI3K mRNA and Akt mRNA was detected by In situ hybridization.Compared with the shamed group, the neurological deficits of themodel group was obvious; The volume of cerebral infarction and theneurons’ swelling were very apparent; the expression of vWF at cerebralischemic penumbra was high, and also happened to the expression of bFGFand the protein and gene expression of PI3K/Akt. The difference wassignificant (P<0.05or P<0.01). Compared with the model group,neurological deficits symptom of SD rats in each Kangnaoye group and thenimodipine group was improved in varying degrees, the neurological scoreof cerebral ischemia-reperfusion in rats reduced to different degrees, also the infarction size and the pathological change, the expression of vWF atcerebral ischemic penumbra was high, and also happened to the proteinexpression of bFGF and the protein and gene expression of PI3K/Akt.There was a significant difference (P <0.05or P <0.01). Compared with thenimodipine group, Kangnaoye high dose group and Kangnaoye mediumdose groups can minimize the neurological score, infarction size and thepathological changes of experimental cerebral ischemia-reperfusion in rats.The expression of vWF, bFGF protein and the protein and gene expressionof PI3K/Akt increased significantly, and the difference was significant(P<0.05or P<0.01). However, there was no significant difference betweenKangNaoYe group of medium dose and high dose(P>0.05), they are muchbetter than the low dose group (P<0.05).Above all, these results suggest that Kangnaoye may regulate theexpression of bFGF, and PI3K/Akt to promote angiogenesis and improveblood supply of the ischemic penumbra, and thus plays a protective effecton the brain.
Keywords/Search Tags:Kangnaoye, Cerebral ischemia-reperfusion injury, microvessel density, bFGF, PI3K/Akt signal transduction pathway
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