丹参酮IIA对新生大鼠缺氧缺血性脑损伤时低氧诱导因子1α基因表达的影响
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Tanshinone IIA Has Effect on Gene Expression of Hypoxia-inducible Factor-1α in Neonatal Rats with Hypoxic-ischemic Brain Damage
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    摘要:

    目的:观察丹参酮IIA(Tanshinone IIA,TSA)对新生大鼠缺氧缺血性脑损伤(Hypoxia ischemic brain damage,HIBD)时低氧诱导因子-1α(Hypoxia-Inducible Factor-1α,HIF-1α)基因表达的影响。方法:7日龄的SD大鼠随机分5组:假手术组、模型组、低剂量治疗组、中剂量治疗组、高剂量治疗组,每组12只,假手术组游离左颈总动脉不结扎,其余组均建立围产期HIBD大鼠模型,低、中、高剂量治疗组TSA用量分别为40 mg/kg、80 mg/kg、160 mg/kg,通过行为学指标观察新生大鼠造模后行为改变,用荧光定量PCR方法检测各组HIF-1α的表达,HE染色方法观察脑组织病理变化,HIF-1α原位免疫组织化学标记染色,显微镜下进行阳性表达对比。结果:假手术组大鼠前后行为无差别,其余各组均出现行为异常,与模型组比较,治疗组的行为恢复快,且TSA剂量越高,恢复越好。与假手术组比较,模型组HIF-1α基因表达明显增多(P<0.05);与模型组比较,治疗组HIF-1α基因表达更多,且剂量越高,HIF-1α表达量越多,差异均有统计学意义(P<0.05)。结论:TSA可能通过上调HIF-1α的表达来保护脑组织,且保护作用和HIF-1α的表达量呈正相关;在一定范围内增加TSA的剂量,可以提高HIF-1α的表达。

    Abstract:

    Objective:To observe the clinical effect of tanshinone IIA(Tanshinone IIA, TSA)for gene expression of hypoxia-inducible factor-1α(Hypoxia-Inducible Factor-1α,HIF-1α)in neonatal rats with hypoxic-ischemic brain damage(Hypoxia ischemic brain damage, HIBD).Methods:Divided seven-day-old SD rats randomly into 5 groups: the sham operation group,the model group,the low-dose treatment group,the medium-dose treatment group,the high-dose treatment group,12 rats in each group.The sham operation group was given no ligature for free left common carotid artery,while other groups were built HIBD model.The doses of TSA in the low-,medium-and high-dose treatment groups were 40 mg/kg,80 mg/kg and 160 mg/kg respectively.Observed the behavioral changes of neonatal rats after modeling by behavioral indexes,detected the expressions of HIF-1α in each group by fluorescence quantitative PCR,and observed the pathological changes of brain tissue through HE staining.Stained HIF-1α with in situ immunohistochemical staining and compared the positive expression under microscope.Results:There was no difference in the behaviors of rats in the sham operation group before and after treatment,and other groups all showed behavioral abnormalities.Compared with the model group,the behavior in the treatment group recovered quickly,and the higher the TSA dose, the better the recovery.Compared with the sham operation group,the expression of HIF-1α gene in the model group was significantly increased(P<0.05);compared with the model group,the HIF-1α gene expression in the treatment group was more,and the higher the dose,the more the expression level of HIF-1α,differences being significant(P<0.05).Conclusion:TSA can protect brain tissue by up-regulating the expression of HIF-1α,and its protective effect is positively correlated with the expression of HIF-1α.The incremental dose of TSA within a certain range can increase the expression of HIF-1α.

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陈晨,王利玲.丹参酮IIA对新生大鼠缺氧缺血性脑损伤时低氧诱导因子1α基因表达的影响[J].新中医,2018,50(12):16-19

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  • 在线发布日期: 2018-12-09
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