姜黄素对慢性脑缺血大鼠脑组织海马CA1区损伤的修复作用及其机制

Repair Effect of Curcumin on Injury of Hippocampal CA1 Area in Rats with Chronic Cerebral Ischemia and Relevant Mechanism

目的探讨姜黄素(Curcumin)对慢性脑缺血大鼠脑组织海马CA1区损伤的修复作用及其机制。方法采用双侧颈总动脉永久性结扎建立慢性脑缺血大鼠模型,术后24 h,将模型大鼠随机分为单纯缺血组、姜黄素高剂量(100 mg/kg)治疗组和姜黄素低剂量(50 mg/kg)治疗组,另设假手术对照组和正常对照组。姜黄素高、低剂量治疗组分别经腹腔注射100和50 mg/kg姜黄素,单纯缺血组、假手术组和正常对照组腹腔注射等量的DMSO,每天1次,连续14 d。给药14 d后,取各组大鼠脑组织,HE染色和尼氏染色观察海马CA1区的形态学变化,免疫组化法观察海马CA1区神经胶质微丝酸性蛋白(Glial fib-rillaryacidic protein,GFAP)和巢蛋白(Nestin)的表达。结果与假手术组相比,单纯缺血组大鼠海马CA1区锥体细胞和尼氏小体丢失,细胞核固缩,星形胶质细胞肥大并大量增生;经姜黄素治疗后,神经元损伤明显减轻,同时伴有GFAP和Nestin阳性细胞大量增加,姜黄素高剂量治疗组与单纯缺血组相比,差异有统计学意义(P<0.05)。结论姜黄素能显著增强慢性脑缺血大鼠脑组织海马CA1区GFAP和Nestin蛋白的表达,减轻神经元损伤,对慢性脑缺血损伤有一定的治疗作用。

Objective To investigate the repair effect of curcumin on injury of hippocampal CA1 area in rats with chronic cerebral ischemia as well as the relevant mechanism.Methods Rat model of chronic cerebral ischemia was established by permanent occlusion of bilateral common carotid arteries（2VO）.The model rats 24 h after operation were divided into 2VO,2VO ＋ curcumin 100 mg / kg and 2VO ＋ curcumin 50 mg / kg groups randomly,using the rats receiving sham operation and normal rats as controls.The rats in 2VO ＋ curcumin 100 mg / kg and 2VO ＋ curcumin 50 mg / kg groups were injected i.p.with curumin,while those in sham operation and normal control groups with an equal volume of DMSO,once a day for 14 d.The brain tissues in various groups were collected and observed for morphology of hippocampal CA1 area by HE staining and Nissl staining,and for expressions of glial fibrillaryacidic protein（GFAP） and Nestin in hippocampal CA1 area by immunohistochemical assay.Results Compared with those in sham operation group,the losses of pyramidal cells and Nissl bodies,shrinkage of nuclei as well as hypertrophy and proliferation in a large quantity of astrocytes were observed in hippocampal CA1 area of rats in 2VO group.After treatment with curcumin,the injury of neuron was relieved significantly,while GFAP-and Nestin-positive cells increased in a large quantity,which showed significant difference in 2VO and 2VO ＋ curcumin 100 mg / kg groups（P 0.05）.Conclusion Curcumin increased the expressions of GFAP and Nestin in hippocampal CA1 area of rats with chronic cerebral ischemia,relieved the injury of neuron and improved the injury caused by chronic cerebral ischemia.