全反式维甲酸对大鼠脑缺血再灌注损伤后MMP-9表达的影响

发布时间：2018-05-21 09:48

本文选题：全反式维甲酸 + 脑缺血再灌注　；参考：《中南大学》2014年硕士论文

【摘要】：目的通过观察全反式维甲酸(all trans retinoic acid,ATRA)对缺血再灌注大鼠基质金属蛋白酶-9(matrix metalloproteinase9, MMP-9)表达的影响,探讨ATRA的神经保护作用及可能机制。方法健康雄性成年SD大鼠180只,随机分为3组,每组60只,即假手术组(Sham组),缺血再灌注手术组(OP组)和ATRA干预组(ATRA组)。Sham组只行颈部手术,不行血管栓塞,ATRA组和OP组按ZeaLonga方法行大脑中动脉栓塞。ATRA组术后每日予以30mg/kgATRA油溶液灌胃,Sham组和OP组每日食用油灌胃。每组分别于造模后1天,3天和7天,行TTC染色、EB染色、免疫组化和Western Blot检测MMP-9。结果 1.神经功能评分 Sham组大鼠无运动功能缺损,Bederson评分均为0分。与OP组比较,ATRA3天组大鼠Bederson评分有显著改善(P0.05),1天组和7天组改善不显著(P0.05)。 2.TTC染色 Sham组大鼠TTC染色未发现梗死区域。OP组1天时脑梗死最明显,3天、7天时梗死体积逐渐减小；和OP组比较,ATRA组各时间点梗死体积均减小,其中1天、7天组有统计学意义(P0.05)。 3.EB含量 Sham组各时间点脑组织EB含量均较低。OP组EB含量再灌注后1天达高峰,后逐渐下降,7天尚未降至Sham组水平。与Sham组相比,OP组大鼠1天、3天、7天各时间点EB含量均显著升高(P0.05)。与OP组相比,ATRA组各时间点EB含量均减少,其中1天组和7天组具有统计学意义(P0.05)。 4.免疫组化 Sham组大鼠脑组织内基本无MMP-9表达。OP组和ATRA组大鼠MMP-9主要在梗死区及梗死区附近的胶质细胞的胞浆中表达。与Sham组相比,OP组MMP-9的表达明显增多,其中3天,7天组具有统计学意义(P0.05)。与OP组比较,ATRA组各时间点MMP-9的表达均减少,其中3天和7天组有统计学意义(P0.05)。 5.Western Blot 与Sham组比较,OP组1天、3天、7天各时间点MMP-9的表达均显著增加(P0.05)。与OP组比较,ATRA组1天、3天和7天组MMP-9表达均显著降低(P0.05)。结论 ATRA减轻MCAO大鼠血脑屏障的损伤,可能机制为通过下调MMP-9的表达。
[Abstract]:Objective To investigate the effects of all trans retinoic acid ( ATRA ) on the expression of matrix metalloproteinase - 9 ( MMP - 9 ) in ischemia - reperfusion rats .

Methods 180 healthy male adult SD rats were randomly divided into three groups : sham operation group ( Sham group ) , ischemia / reperfusion group ( OP group ) and ATRA group ( ATRA group ) . The Sham group only underwent cervical operation , no vascular embolism , ATRA group and OP group were injected into the middle cerebral artery embolization according to ZeaLonga method . All groups were treated with 30 mg / kg ATRA oil solution for 1 day , 3 days and 7 days , TTC staining , EB staining , immunohistochemistry and Western Blot were used to detect MMP - 9 .

Results

1 . Nerve function score

Compared with OP group , the score of Bederson ' s score in ATRA3 - day group was significantly improved ( P0.05 ) , and the improvement of group 1 - day group and 7 - day group was not significant ( P0.05 ) .

2 . TTC Staining

The infarct area was not found in the control group of the Sham group . The cerebral infarction was the most obvious in OP group at 1 day , and the infarct volume was gradually decreased in 3 days and 7 days .
Compared with OP group , the infarct volume decreased at all time points of ATRA group , among which 1 day and 7 day group had statistical significance ( P0.05 ) .

3.EB Content

Compared with Sham group , the EB content of all time points in OP group increased significantly ( P0.05 ) . Compared with the Sham group , the EB content in all time points in OP group decreased significantly ( P0.05 ) .

4 . Immunohistochemical technique

Compared with Sham group , the expression of MMP - 9 in OP group was significantly higher than that in Sham group ( P0.05 ) .

5.Western Blot

Compared with Sham group , the expression of MMP - 9 was significantly increased in OP group 1 day , 3 day and 7 days ( P0.05 ) . Compared with OP group , the expression of MMP - 9 in group 1 , 3 and 7 days in ATRA group was significantly decreased ( P0.05 ) .

Conclusion

ATRA reduces the damage of blood - brain barrier in the rats with middle cerebral artery occlusion , which may be mediated by downregulating the expression of MMP - 9 .
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.3

【参考文献】