白藜芦醇对慢性脑缺血大鼠认知损伤和海马MMP-9和TIMP-1表达的影响研究

Study on effects of resveratrol on cognitive damage and expression of hippocampus MMP-9 and TIMP-1 in chronic cerebral ischemia rats

目的探讨白藜芦醇(RES)对大鼠慢性脑缺血认知功能损伤和海马区基质金属蛋白(MMP)-9mRNA、基质金属蛋白酶抑制剂(TIMP)-1mRNA表达的影响。方法将32只雄性SPF级Wistar大鼠分为假手术组(Sham组,8只)、模型组[双侧颈动脉闭塞(BCCA)组,8只]、20mg·kg-1·d-1 RES组(RES-L组,8只)和40mg·kg-1·d-1 RES组(RES-H组,8只)。实验第1天采用BCCA法建立慢性脑缺血大鼠模型。实验第1～42天不间断RES腹腔给药。实验第35天行旷场实验,实验第36～41天行Morris水迷宫实验。实验第42天采用RT-PCR技术检测大鼠海马MMP-9mRNA和TIMP-1mRNA表达变化。结果认知功能方面,与Sham组相比,BCCA组、RES-L组和RES-H组均表现出不同程度的焦虑样行为增多、上台潜伏期延长和穿格次数减少(P<0.05),RES-H组以上症状程度较与BCCA组和RES-L组明显改善,差异有统计学意义(P<0.05)。海马区MMP-9mRNA表达方面,BCCA组、RES-L和RES-H组较Sham组均有不同程度表达升高(P<0.05),但RES-H组表达量升高程度低于BCCA组和RES-L组(P<0.05)。海马区TIMP-1mRNA表达方面,BCCA组、RES-L和RES-H组较Sham组均有不同程度表达升高(P<0.05),但RES-H组表达量升高程度高于BCCA组和RES-L组(P<0.05)。结论慢性脑缺血预防性给予RES干预对大鼠认知功能损害有一定的保护作用,其机制可能与RES参与海马区MMP-9表达抑制、TIMP-1表达促进有关。

Objective To study the effect of resveratrol(RES)on the cognitive impairment and the expression of MMP-9 mRNA and TIMP-1 mRNA in the hippocampus of chronic cerebral ischemia rats.Methods Thirty-two male Wistar rats(SPF grade)were randomly divided into the Sham operation group(Sham group),model group(BCCA group),20 mg·kg^-1·d^-1 RES group(RES-L group)and 40 mg·kg^-1·d^-1 RES group(RES-H group),8 cases in each group.The chronic cerebral ischemia rat models were established by adopting the bilateral common carotid artery occlusion(BCCA)on 1 d of the experiment.RES was uninterruptedly given by intraperitoneal injection during 1-42 d of experiment.The open field test was conducted on 35 d and the Morris water maze test was conducted on 36-41 d.Then RT-PCR was adopted to measure the expression changes of MMP-9 mRNA and TIMP-1 mRNA in hippocampus on 42 d of experiment.Results In the aspect of cognitive function,compared with Sham group,the different degrees of anxiety behaviors in the BCCA group,RES-L group and RES-H group were increased,the latent period of going up onto the platform was extended and the times of crossing the platform were decreased(P<0.05).The degree of above symptoms in the RES-H group was significantly improved compared with the BCCA group and RES-L group,and the difference was statistically significant(P<0.05).In the aspect of expression of MMP-9 mRNA in the hippocampus area,the expression in the BCCA group,RES-L group and RES-H group had different degrees of increase compared with the Sham group(P<0.05).However,the increasing level in the RES-H group was significantly lower than that in the BCCA group and RES-L group(P<0.05).In the aspect of expression of TIMP-1 mRNA in the hippocampus area,compared with Sham group,the BCCA group,RES-L group and RES-H group had different degrees of expression increase(P<0.05).However,the increasing level in the RES-H group was higher than that in the BCCA group and RES-L group(P<0.05).Conclusion Prophylactically giving RES in chronic cerebral ischemia has a certain protective effect on rat cognitive function impairment,and its mechanism may be related to RES participating in the inhibition of MMP-9 expression and the promotion of TIMP-1 expression in the hippocampus area.