摘要
目的探讨原花青素(PC)对2型糖尿病局灶性脑缺血大鼠脑信号转导及转录激活因子1(STAT1)表达的影响。方法 75只SD大鼠随机分为假手术组,2型糖尿病合并脑缺血组,PC低、中、高剂量组,每组15只。制作2型糖尿病大鼠局灶性脑缺血模型,PC组在建立2型糖尿病模型后给予灌胃,1次/24 h,连续1周,于大脑中动脉缺血术前1 h再灌胃1次。PC低、中、高剂量组分别以PC粉剂50、100、200 mg/(kg·次)灌胃。进行神经功能评分,免疫组化SABC染色法对STAT1蛋白进行定量分析,统计大鼠缺血侧大脑皮质缺血半暗带区每高倍镜视野STAT1蛋白的阳性细胞数。结果与假手术组比较,2型糖尿病合并脑缺血组的神经行为学评分明显增高[0分比(3.42±1.00)分],缺血侧海马区神经细胞计数减少[(102.10±4.62)个/HP比(56.60±6.15)个/HP],缺血侧皮质STAT1阳性细胞数增多[(4.10±1.26)个/HP比(20.13±1.36)个/HP],差异均有高度统计学意义(均P<0.01);与2型糖尿病局灶性脑缺血组相比,PC低、中和高剂量组的神经行为学评分明显减少[(2.83±0.83)、(1.83±0.58)、(1.42±0.51)分]、缺血侧海马区神经细胞计数增多[(82.40±2.88)、(92.40±4.28)、(95.20±5.26)个/HP]、缺血侧皮质STAT1的表达均明显减少[(17.25±0.99)、(13.67±1.88)、(12.92±1.74)个/HP],差异均有统计学意义(P<0.05或P<0.01);PC中、高剂量组的作用比PC低剂量组更明显(P<0.01),但PC中、高剂量组组间比较,差异无统计学意义(P>0.05)。结论原花青素可能通过降低STAT1蛋白的表达,影响Janus激酶/信号转导及转录激活因子信号转导途径,从而抑制细胞凋亡,减轻神经功能缺损,达到对2型糖尿病合并缺血性脑血管病的保护作用。
Objective To investigate the effect of procyanidin （PC） on the expression of signal transducers and activators of transcription （STAT1） in SD rats with type 2 diabetes mellitus and focal cerebral ischemia.Methods 75 SD rats were randomly divided in to sham operation group,SD rats with type 2 diabetes mellitus and focal cerebral ischemia group,PC low-dose group,PC middle-dose group,and PC high-dose group,with 15 rats in each group.Set up type 2 diabetes mellitus-MCAO model,rats of the PC groups were treated with intragastric administration of PC after creation of the diabetes model,once a day for 1 week,and at 1 hour before the MCAO surgery,rats were treated with intragastric administration once again.The doses of PC for low-dose,mid-dose and high-dose groups were 50,100,200 mg/（kg·time）.The neurological function was evaluated,the STAT1 protein was quantitative analyzed by immunohistochemistry methods,and the neurons of the ischemicat lateral hippocampus of high magnification every vision in ischemic penumbra were counted.Results Compared with sham group,neurologic impairment score of SD rats with type 2 diabetes mellitus and focal cerebral ischemia group increased [0 score vs （3.42±1.00） scores],the neurons of ischemical lateral hippocampus decreased [（102.10±4.62）/HP vs （56.60±6.15）/HP],the expression of STAT1 increased [（4.10±1.26）/HP vs （20.13±1.36）/HP],the differents were statistically significant （P ＜ 0.01）; compared with SD rats with type 2 diabetes mellitus and focal cerebral ischemia group,neurologic impairment score decreased [（2.83±0.83）,（1.83±0.58）,（1.42±0.51） scores],the neurons of ischemical lateral brain increased [（82.40±2.88）,（92.40 ±4.28）,（95.20 ±5.26）/HP],the expression of STAT1 decreased [（17.25±0.99）,（13.67±1.88）,（12.92±1.74）/HP],the differences were statistically significant （P ＜ 0.05 or P ＜ 0.01）,whereby the mid-dose and high-dose groups showed a more substantial decrease compared with （P ＜ 0.01）,but with no statistically significant difference in the two groups （P ＞ 0.05）.Conclusion These results indicate that PC has a neuroprotective effect on type 2 diabetes mellitus with focal cerebral ischemia; this may be through decreasing the expression of STAT1,which influences the Janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway that may inhibit apoptosis to relieve neurological impairment.
出处
《中国医药导报》
CAS
2014年第9期33-36,40,共5页
China Medical Herald
关键词
糖尿病
脑缺血
原花青素
转录激活因子1
Type 2 diabetes mellitus
Cerebral ischemia
Procyanidin
STAT1
