维甲酸对弹性蛋白酶诱导的大鼠肺气肿的干预作用及其与MMP-9和TIMP-1变化之间的关系  

Prophylactic effect of retinoic acid on elastase-induced emphysema in rats and relationship with expression of MMP-9 and TIMP-1

作　　者：程青[1] 王秋月[2] 许惟元[2] 

机构地区：[1]沈阳市第五人民医院呼吸科,辽宁沈阳110023 [2]中国医科大学第一附属医院呼吸疾病研究所,辽宁沈阳110001

出　　处：《中国现代医学杂志》2008年第15期2149-2151,2155,共4页China Journal of Modern Medicine

摘　　要：目的观察维甲酸对弹性蛋白酶诱导的大鼠肺气肿的干预作用及其与MMP-9和TIMP-1变化之间的关系,探讨维甲酸可能的作用机制。方法雄性Wistar大鼠21只,随机分为3组:对照组、模型组和维甲酸组,每组7只。模型组及RA组大鼠气管内滴入弹性蛋白酶复制肺气肿模型,RA组同时给予RA腹腔注射进行干预。25d后,光镜观察各组大鼠肺组织的病理改变,计算机辅助图像分析系统测量肺组织石蜡切片中平均肺泡数、平均肺泡面积、平均内衬间隔,免疫组化方法观察各组大鼠肺组织基质金属蛋白酶(MMP-9)及其组织抑制因子(TIMP-1)的蛋白表达情况。结果模型组与对照组比较,平均内衬间隔(MLI)、平均肺泡面积(MAA)增加(P<0.01),平均肺泡数(MAN)减少(P<0.01)。模型组MMP-9和TIMP-1的表达与对照组比较明显增强(P<0.01),且MMP-9/TIMP-1比值失衡;RA组与模型组比较,平均内衬间隔(MLI)、平均肺泡面积(MAA)减少(P<0.01)、平均肺泡数(MAN)增加(P<0.01)。维甲酸组MMP-9和TIMP-1的表达与模型组比较明显减少(P<0.01)。结论维甲酸能够抑制弹性蛋白酶诱导的肺气肿的发生和发展,可使肺气肿时增多的MMP-9、TIMP-1下降,使其比值趋于平衡。[Objective] To evaluate the effect and mechanism of retinoie acid （RA） in preventing elastase-induced emphysema in rats and observe the relation with the expression of MMP-9 and TIMP-1. [Methods] Twentyone Wistar rats were randomly divided into three groups, the normal group, the model group and the RA preventive group, seven rats in each group. The model group and the RA group were established by intratracheal instillation elastase, and the RA group was treated with RA intraperitoneaUy. Twenty-five days later, the pathological changes were observed, mean alveolu number（MAN）, mean alveolu area （MAA）, mean linear intercept （MLI） were measured by computer imaging analysis system, the expression of metaUoproteinase-9（MMP-9） and its tissue inhibitor （TIMP- 1） in the lung tissue were verified by immunohistochemical analysis. [Results] Compared with normal group, MLI and MAA significantly increased （P 〈0.01）, MAN significantly decreased in model group （P 〈0.01）, the expression of MMP-9 and TIMP-1 were significantly increased （P 〈0.01）, and the ratio of MMP-9/TIMP-1 was imbalanced. Compared with model group, MLI and MAA significantly decreased （P 〈0.01）, MAN significantly increased in RA group （P 〈0.01）, the expression of MMP-9 and TIMP-1 were significantly decreased （P 〈0.01）.[Conclusion] Retinoic acid may prevent the development of pulmonary emphysema in rats, decrease the expression of MMP-9 and TIMP-1 and make the ratio of MMP-9/TIMP-1 tend to balance.

关 键 词：实验性肺气肿 基质金属蛋白酶-9 基质金属蛋白酶组织抑制因子-1 弹性蛋白酶 维甲酸 

分 类 号：R-332[医药卫生]