槲皮素对糖尿病脑梗死大鼠脑纤溶激活系统基因表达的研究

The effects of quercetin on expression of t-PA mRNA,u-PA mRNA,PAI-1 mRNA and NSP mRNA in diabetic rats with cerebral infarction

目的观察槲皮素对糖尿病脑梗死大鼠脑组织中纤溶酶原激活物(t-PA)及其抑制剂mRNA表达的影响。方法 Wistar大鼠50只,随机分为正常假手术组、糖尿病假手术组、糖尿病脑梗死组、低剂量与高剂量槲皮素预处理组5组。后4组大鼠制作糖尿病模型。造模后低剂量与高剂量槲皮素预处理组分别按体质量予槲皮素50 mg/(kg.d)、100 mg/(kg.d)灌胃15 d,并与糖尿病脑梗死组行自体血栓脑梗死处理。以半定量反转录-聚合酶链式反应法(RT-PCR)检测各组动物脑组织中组织型纤溶酶原激活物(t-PA)mRNA、尿激酶型纤溶酶原激活物(u-PA)mRNA、1型纤溶酶原激活物抑制剂(PAI-1)mRNA、神经丝氨酸蛋白酶抑制剂(NSP)mRNA的表达并进行分析比较。结果与糖尿病脑梗死组t-PA mRNA、PAI-1 mRNA相对表达量(分别为0.27±0.03、0.68±0.06)比较,低剂量、高剂量槲皮素预处理组t-PA mRNA表达(分别为0.32±0.05、0.44±0.10)升高,PAI-1 mRNA表达(0.53±0.15、0.32±0.07)降低(均P<0.01),高剂量、低剂量槲皮素预处理组、糖尿病脑梗死组之间u-PA mRNA、NSP mRNA表达无统计学差异。结论槲皮素可能通过促进t-PA mRNA表达、抑制PAI-1 mRNA表达改善糖尿病脑梗死大鼠纤溶功能。槲皮素预处理对糖尿病脑梗死大鼠u-PA mRNA、NSP mRNA表达无明显影响。

Objective To observe the influences of quercetin on the mRNA expressions of plasminogen activators and plasminogen activator inhibitors in diabetic rats with cerebral ischemia.Methods Fifty Wistar rats were randomly divided into five groups： the normal sham operation group,the diabetic sham operation group,the diabetic cerebral infarction group without treatment,the diabetic cerebral infarction groups with low dose or high dose of quercetin pretreatment.Diabetes was induced in the rat groups except the normal sham operation group.Then,the rats in low and high doses of quercetin pretreatment groups were treated with intragastric administration of quercetins,50 mg/（kg·d） and 100 mg/（kg·d） respectively,for 15 days.At last,cerebral infarct model was done in rats in the diabetic cerebral infarction group,low and high doses of quercetin pretreatment groups.The mRNA expressions of tissue-type plasminogen activator（t-PA）,urokinase-type plasminogen activator（u-PA）,plasminogen activator inhibitor（PAI-1） and neuroserpin（NSP） in the brain tissues were detected with reverse transcription-polymerase chain reaction（RT-PCR）.The measured parameters were compared among the different groups.Results Compared with the normal sham operation group and diabetic sham operation group,there were significant changes,including the expressions of t-PA mRNA、u-PA mRNA、PAI-1 mRNA、NSP mRNA,in the diabetic cerebral infarction group,the low dose of quercetin pretreatment group and the high dose of quercetin pretreatment group（all P0.01）.Compared with the diabetic cerebral infarction group（0.27±0.03,0.68±0.06,respectively）,the expression of t-PA mRNA in the low and high doses of quercetin pretreatment groups（0.32±0.05,0.44±0.10,respectively） increased significantly（both P0.01）.Compared with the diabetic cerebral infarction group,the expression of PAI-1 mRNA in the low and high doses of quercetin pretreatment groups（0.53±0.15,0.32±0.07,respectively）decreased significantly（both P0.01）.There were no significant differences in the expressions of u-PA mRNA and NSP mRNA among the diabetic cerebral infarction group,the low and high doses of quercetin pretreatment groups.Conclusions Quercetin could improve the fibrinolytic function in cerebral infarction by promoting the expression of t-PA mRNA and restraining the expression of PAI-1 mRNA.Quercetin pretreatment had no significantly effect on the expressions of u-PA mRNA and NSP mRNA in the diabetic rats with cerebral infarction.