半枝莲总黄酮对大鼠脑缺血再灌注损伤的保护作用
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摘要
目的:探讨半枝莲总黄酮对大鼠脑缺血再灌注损伤的保护作用及作用机制。方法:45只健康雄性SD大鼠按照随机数字表法分为假手术组、模型组和半枝莲组,每组15只。模型组和半枝莲组均制备大鼠脑缺血再灌注损伤模型。半枝莲组每日给予半枝莲总黄酮(140 mg·kg~(-1))灌胃,其余两组每日灌服等量的生理盐水,共干预4周。末次给药后处死大鼠,采集脑组织,采用2,3,5-氯化三苯基四氮唑(triphenyltetrazolium chloride,TTC)染色法检测脑梗死体积;采用HE染色法观察大鼠海马区脑组织形态学变化。采用免疫组织化学法检测各组大鼠脑组织立早基因(FBJ osteosarcoma oncogene,c-fos)、B-细胞淋巴瘤/白血病-2基因家族蛋白(B cell lymphoma/lewkmia-2,Bcl-2)相关X蛋白(Bcl-2 associated X protein,BAX)的表达。结果:TTC结果显示:模型组脑梗死体积最大,半枝莲组梗死体积显著减小(P<0.05)。病理组织学结果显示:模型组脑梗死表现最明显,而半枝莲组的脑梗死程度有所减轻。免疫组织化学显示:与假手术组比较,模型组和半枝莲组大鼠脑组织c-fos和Bax蛋白表达升高,Bcl-2蛋白表达下降(P<0.05);与模型组比较,半枝莲组大鼠脑组织c-fos和Bax蛋白表达下降,Bcl-2蛋白表达升高(P<0.05)。结论:半枝莲总黄酮治疗脑缺血再灌注损伤的可能机制与其下调c-fos和Bax表达、上调Bcl-2表达有关。
Objective: To explore the protective effect and mechanism of total flavonoids of Scutellaria barbata on cerebral ischemiareperfusion injury in rats. Methods: 45 healthy SD male rats were divided into sham operation group,model group and scutellaria barbata group according to the random number table method,with 15 cases in each group. Rat models of cerebral ischemia-reperfusion injury were established in both model group and Scutellaria barbata group. The rats in scutellaria barbata group were lavaged with total flavonoids of Scutellaria barbata( 140 mg·kg-1) everyday,and the rats of the other two groups were given the same amount of normal saline everyday,with a total of 4 weeks of intervention. After the last administration,rats were killed and brain tissue was collected,cerebral infarction volume was detected using the 2,3,5-triphenyltetrazolium chloride( TTC) staining method,and the morphological changes of hippocampus in rats were observed by HE staining. The expressions of FBJ osteosarcoma oncogene( c-fos),B cell lymphoma/lewkmia-2( Bcl-2),Bcl-2 associated X protein( BAX) in brain tissue of rats in each group were detected by Immunohistochemical method. Histopathological results showed that the cerebral infarction was the most obvious in the model group,while the degree of cerebral infarction was reduced in the Scutellaria barbata group. Results: The TTC results showedthat the cerebral infarction volume was the largest in the model group and the infarct volume was significantly decreased in the Scutellaria barbata group( P < 0. 05). Immunohistochemistry showed that compared with the sham operation group,the expression of c-fos and Bax protein in the brain tissue of the model group and the Scutellaria barbata group increased,and the expression of Bcl-2 protein decreased( P < 0. 05). Compared with the model group,the expression of c-fos and Bax protein in the brain tissue of rats in the Scutellaria barbata group decreased,and the expression of Bcl-2 protein increased( P < 0. 05). Conclusion: The possible mechanism of total flavonoids of Scutellaria barbata on cerebral ischemia-reperfusion injury is related to down-regulation of c-fos and Bax expression and up-regulation of Bcl-2 expression.
Objective: To explore the protective effect and mechanism of total flavonoids of Scutellaria barbata on cerebral ischemiareperfusion injury in rats. Methods: 45 healthy SD male rats were divided into sham operation group,model group and scutellaria barbata group according to the random number table method,with 15 cases in each group. Rat models of cerebral ischemia-reperfusion injury were established in both model group and Scutellaria barbata group. The rats in scutellaria barbata group were lavaged with total flavonoids of Scutellaria barbata( 140 mg·kg-1) everyday,and the rats of the other two groups were given the same amount of normal saline everyday,with a total of 4 weeks of intervention. After the last administration,rats were killed and brain tissue was collected,cerebral infarction volume was detected using the 2,3,5-triphenyltetrazolium chloride( TTC) staining method,and the morphological changes of hippocampus in rats were observed by HE staining. The expressions of FBJ osteosarcoma oncogene( c-fos),B cell lymphoma/lewkmia-2( Bcl-2),Bcl-2 associated X protein( BAX) in brain tissue of rats in each group were detected by Immunohistochemical method. Histopathological results showed that the cerebral infarction was the most obvious in the model group,while the degree of cerebral infarction was reduced in the Scutellaria barbata group. Results: The TTC results showedthat the cerebral infarction volume was the largest in the model group and the infarct volume was significantly decreased in the Scutellaria barbata group( P < 0. 05). Immunohistochemistry showed that compared with the sham operation group,the expression of c-fos and Bax protein in the brain tissue of the model group and the Scutellaria barbata group increased,and the expression of Bcl-2 protein decreased( P < 0. 05). Compared with the model group,the expression of c-fos and Bax protein in the brain tissue of rats in the Scutellaria barbata group decreased,and the expression of Bcl-2 protein increased( P < 0. 05). Conclusion: The possible mechanism of total flavonoids of Scutellaria barbata on cerebral ischemia-reperfusion injury is related to down-regulation of c-fos and Bax expression and up-regulation of Bcl-2 expression.
引文
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[17]孙恺,张秀萍,宋林杰,等.糖尿病合并脑缺血再灌注损伤小鼠模型制作及其炎症因子表达分析[J].中华神经医学杂志,2016,15(2):123-129.
[18]吴晓光,檀荣方,杨岚,等.山楂叶总黄酮对慢性脑缺血大鼠脑组织c-fos、Bcl-2蛋白表达的影响[J].中国老年学杂志,2016,36(1):33-34.
[2]褚忠海,王文静,韩丽珠,等.皮质下缺血性脑血管病患者血清sICAM-1、IGF-1水平与认知损害的关系[J].安徽医科大学学报,2016,51(2):268-271.
[3]BILGIC M,ALTUN G,CAKICI H,et al.The protective effect of Montelukast against skeletal muscle ischemia reperfusion injury:An experimental rat model[J].Ulus Travma Acil Cerrahi Derg,2018,24(3):185-190.
[4]白娟,禄保平,江若霞.保肝解毒颗粒对急性肝损伤小鼠肝细胞Bcl-2、Bax表达的影响[J].中医学报,2016,31(10):1549-1553.
[5]李娅,张睿智,杨华林,等.高压氧预处理对急性减压所致的大鼠肺组织细胞凋亡及Bcl-2/Bax表达的影响[J].现代生物医学进展,2017,17(3):401-404.
[6]马霄,邵南齐,陈晓敏,等.半枝莲总黄酮对反复脑缺血再灌注小鼠脑能量代谢的影响[J].吉林中医药,2015,35(4):399-401.
[7]HENTIA C,RIZZATO A,CAMPORESI E,et al.An overview of protective strategies against ischemia/reperfusion injury:The role of hyperbaric oxygen preconditioning[J].Brain Behav,2018,8(5):e00959.
[8]崔小英,于建设,都义日,等.脑缺血再灌注损伤及脑保护药物研究进展[J].河北医药,2016,38(4):596-600.
[9]赵铁华,邓淑华,杨鹤松,等.半枝莲总黄酮抗甲型H1N1流感病毒感染的药效学研究[J].中国药理学通报,2014,30(1):147-148.
[10]郭可,缪红,王树松,等.半枝莲黄酮抑制复合Aβ所致大鼠皮层细胞NFT沉积及其调节机制[J].中国病理生理杂志,2016,32(12):2147-2156.
[11]KE F F S,VANYAI H K,COWAN A D,et al.Embryogenesis and Adult Life in the Absence of Intrinsic Apoptosis Effectors BAX,BAK,and BOK[J].Cell,2018,173(5):1217-1230.
[12]ZHANG Y,ISHIDA CT,SHU C,et al.Inhibition of Bcl-2/Bcl-xL and c-MET causes synthetic lethality in model systems of glioblastoma[J].Sci Rep,2018,8(1):7373.
[13]王日康,张浪,陈河如.藏红素在体保护大鼠脑缺血/再灌注损伤和可能的作用机制[J].中山大学学报(自然科学版),2018,57(2):143-154.
[14]CHEN X,SHEN J,WANG Y,et al.Up-Regulation of c-Fos Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage[J].Cell Mol Neurobiol,2015,35(3):363-376.
[15]BAI L,MAO R,WANG J,et al.ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins[J].Med Oncol,2015,32(3):57.
[16]XIAO P,LIU X W,ZHAO N N,et al.Correlations of neuronal apoptosis with expressions of c-Fos and c-Jun in rats with post-ischemic reconditioning damage[J].Eur Rev Med Pharmacol Sci,2018,22(9):2832-2838.
[17]孙恺,张秀萍,宋林杰,等.糖尿病合并脑缺血再灌注损伤小鼠模型制作及其炎症因子表达分析[J].中华神经医学杂志,2016,15(2):123-129.
[18]吴晓光,檀荣方,杨岚,等.山楂叶总黄酮对慢性脑缺血大鼠脑组织c-fos、Bcl-2蛋白表达的影响[J].中国老年学杂志,2016,36(1):33-34.