姜黄素在脑血流低灌注致血管性痴呆青年鼠和老年鼠中的作用及差异比较

Curcumin reduce brain damage and improve cognitive dysfunction of vascular dementia rats in dose-dependent manner without age difference

目的:观察姜黄素(curcumin)对脑血流低灌注所致血管性痴呆(vascular dementia,VD)青年鼠和老年鼠学习记忆能力以及海马组织形态学的影响,并进一步观察比较姜黄素对VD的疗效是否有年龄差异性。方法:分别将50只青年及50只老年Sprague-Dawley(SD)大鼠随机分为正常对照组、假手术组、单纯缺血组(2VO)组、低剂量组(curcumin,50 mg/kg)及高剂量组(100mg/kg),每组各10只,采用永久性双侧颈总动脉结扎法(2VO法)制备VD模型。药物治疗组于术后24 h开始每日腹腔注射curcumin,连续给药30 d;采用Morris水迷宫实验测试两个年龄段各组大鼠的学习和空间记忆能力变化;采用HE染色和尼氏(Nissl)染色观察两个年龄段各组大鼠海马CA1区组织形态学改变。结果:Morris水迷宫试验表明,脑血流低灌注可导致老年大鼠及青年大鼠学习记忆能力下降(P<0.05),经姜黄素处理后学习记忆能力均明显改善(P<0.05);HE染色及尼氏染色显示脑血流低灌注可导致老年及青年VD大鼠海马CA1区出现病理形态学改变,姜黄素能减轻老年及青年VD大鼠海马CA1区的病理形态学改变;但2个年龄段大鼠间的学习记忆能力及病理改变差异无统计学意义(P>0.05)。结论:姜黄素能减轻老年及青年VD大鼠的脑损伤并改善认知功能障碍,其治疗效果具有一定的量效关系,但无年龄差异性;减轻海马组织的病理性损伤可能是姜黄素改善VD大鼠认知功能障碍的机制之一。

Objective：To observe the effect of curcumin on learning and memory ability and the morphology of the hippocampus of young and aged rats with vascular dementia（VD）induced by cerebral hypoperfusion, then to further explore if the effect of curcumin has any difference in different ages. Methods：Both young and aged rats were randomly divided into normal group,sham-operated group,2VO group,2VO＋curcumin 50 mg/kg group and 2VO＋curcumin 100 mg/kg group（10 rats in each group）. Permanent occlusion of bilateral common carotid arteries ligation（2VO） method was used to set up cerebral ischemia model. The rats were injected intraperitoneally with curcumin or DMSO once daily for 30 d. The changes of learning and memory ability of rats were tested in the Morris water maze;the pathological changes of CA1 region of the hippocampus were measured by HE and Nissl staining. Results：Morris water test showed that 2VO method could reduce learning and memory of young and aged VD rats（P〈0.05）,while curcumin could improve them（P〈0.05）. HE and Nissl staining results showed that 2VO method led to pathological changes of CA1 region in young and aged VD rats（P〈0.05）,and curcumin could reduce the injury（P〈0.05）. No notable difference was found between rats at different ages（P〈0.05）. Conclusion：Curcumin can reduce the brain damage in young and aged VD rats and improve cognitive dysfunction,and the effect was dose-dependent,without age difference. Our study suggests that the pathological injury of the hippocampus might be one of the mechanisms of curcumin on improving cognitive impairment of VD rats.