【摘要】 背景:氟桂嗪和转化生长因子β(TGF-β)都具有抗脑缺血损伤作用,但两者之间是否存在某种联系,目前还不明确。目的:通过研究氟桂嗪对沙鼠脑缺血再灌注后脑内转化生长因子I型,II型受体(TβRI,II)基因表达的影响,探讨氟桂嗪与TGFβ信号转导途径在抗脑缺血损伤方面的联系。设计:随机对照的实验研究。地点和对象:实验在中南大学湘雅二医院中心实验室完成。健康雄性蒙古沙鼠60只,9月龄,体质量(90±5)g,随机分为脑缺血组、氟桂嗪治疗组、假手术组、正常对照组,其中脑缺血组、氟桂嗪治疗组各有缺血再灌6h,1,3,7d组,共计10组,每组6只。干预:夹闭双侧颈总动脉法制作沙鼠脑缺血再灌注模型,氟桂嗪治疗组实验前1d给沙鼠喂食氟桂嗪犤按20mg/(kg·d)犦。采用原位杂交检测TβRI,II基因表达情况,用苏木精-伊红染色方法观察脑组织病理变化。主要观察指标:脑组织病理变化,及脑内TβRI,IImRNAs的表达。结果:氟桂嗪治疗组在再灌注各个时间点脑组织损伤程度均明显轻于脑缺血组。各组沙鼠脑组织的神经元和胶质细胞胞浆均有TβRI,IImRNAs阳性表达。棕褐色颗粒主要位于神经元和胶质细胞胞浆中,但表达程度有所不同。假手术组的TβRI,IImRNAs的表达较正常对照组稍高但无明显差异(P>0.05)。氟桂嗪治疗组中缺血再灌注6h,1d,3dTβRI,IIm更多还原

【Abstract】 BACKGROUND:Both flunarizine and transforming growth factor beta (TGF-β) can protect brain tissue against cerebral ischemia injury. The relation between flunarizine and TGFβis still indefinite at present. OBJECTIVE:To study the effect of flunarizine on mRNA expression of Type I and II receptor of TGF-βTβRⅠand TβRⅡin the brain tissue of gerbils with cerebral ischemia.To demonstrate the relationship between flunarizine and TGF-βsignal transduction pathway against cerebral ischemia injury DESIGN:A randomized controlled experimental research. SETTING and MATERIALS:This experiment was performed in the Central Laboratory of the Second Xiangya Hospital,Central South University.Sixty healthy Mongolian male gerbils of 9 months old, weighing(90±5)g,were divided randomly into four groups:Normal control group,sham-operation group,cerebral ischemia group and flunarizine therapy group.There were cerebral reperfusion 6 hours, 1day,3 days,7 days subgroups in cerebral ischemia group and flunarizine therapy group.There were 10 groups in total with 6 gerbils in each group INTERVENTIONS:Cerebral ischemia reperfusion model of gerbils was established by clipping of the common carotid arteries on both sides. The gerbils in flunarizine therapy group were fed with flunarizine 1 day before experiment(20 mg/ kg per day).Hybridization in situ was used to test genetic expression of TβRI,II.Hematoxyline-eosin staining was used to observe pathological change of brain tissue. MAIN OUTCOME MEASURES:Pathological change of brain tissue and expression of TβRI,II mRNAs in brain tissue. RESULTS:In flunarizine therapy group,the degree of injury of brain tissue was significantly lighter than that at each time in cerebral ischemia group.Positive expression of TβRI,II mRNAs was revealed in neurons and cytoplasm of glial cell of brain tissue in all groups. Brown granules mainly existed in neuron and cytoplasm of glial cell. But the degree of expression was different.The expression of TβRI,II mRNAs in sham-operation group was slightly higher,but there was no significant difference,compared with normal control group (P >0.05).The expression of TβRI,II mRNAs was slightly higher in flunarizine therapy group at reperfusion 6 hours,1day,3 days,but there was no significant difference,compared with cerebral ischemia group (P >0.05).At 7 days,TβRI mRNAs expression decreased (the number of positive cells in 1 000 cells were 85.23±1.71 to 78.87±1.48 (P< 0.01),and TβRII mRNAs expression increased (the number of positive cells in 1 000 cells were 49.28±2.32 to 75.40±2.19 (P< 0.01). CONCLUSION: Flunarizine can inhibit over-expression of TβRI mRNAs after ischemia reperfusion and avoid lopsided development of expression of TβRI and II mRNAs. This may be advantageous to the signal transduction of TGF-βand protect cerebral cells from cerebral ischemic reperfusion injury.更多还原