三叶青水提物对慢性阻塞性肺疾病MMP－9和TIMP－1的影响

目的：观察三叶青水提物对慢性阻塞性肺疾病（COPD）大鼠基质金属蛋白酶9（Matrix met alloproteinases－9，MMP－9）和基质金属蛋白酶抑制剂－1（Matrix met alloproteinases inhibitor－1，TIMP－1）的影响，探讨三叶青对大鼠肺组织的作用机制。方法选择烟熏加气管内滴注内毒素（ LPS）法复制COPD模型，将清洁级健康SD雄性大鼠30只，随机分为3组分别为对照组、模型组和三叶青组，每组10只。造模成功后肺组织采用HE染色观察病理改变，采用免疫组织化学方法测定大鼠肺组织中MMP－9和TIMP－1的表达，酶联免疫吸附法测定大鼠血清、支气管肺泡灌洗液和肺匀浆组织中MMP－9和TIMP－1的表达。结果光学显微镜下可见三叶青组大鼠炎症较模型组有所减轻。酶联免疫吸附法检测结果显示，模型组大鼠肺组织、血清和支气管肺泡灌洗液中MMP－9和TIMP－1含量较对照组显著增加（ P＜0．05），三叶青组的MMP－9和TIMP－1含量较模型组显著下降（P＜0．05）。免疫组织化学检测结果显示，与对照组比较模型组肺组织中的MMP－9和TIMP－1表达明显增多，差异有统计学意义（P＜0．05）。与模型组比较三叶青组肺组织中的MMP－9和TIMP－1表达减少，差异有统计学意义（P ＜0．05）。结论三叶青可能通过下调MMP－9、TIMP－1表达，调节MMP－9／TIMP－1失衡，进而干预气道重塑，延缓病变进展，这可能是其治疗COPD的作用机制之一。

InfIuence of the Water Extract of Radix Tetrastigmae on MMP-9 and TIMP-1 in Rats of Chronic Obstructive PuImonary Disease

ABSTRACT:OBJECTIVE To investigate the effect of water extract of radix tetrastigmae on the matrix metallopro -teinases-9 (MMP-9) and matrix met alloproteinases inhibitor-1(TIMP-1) on chronic obstructive pulmonary disease
( COPD) in rats.METHODS The model of chronic obstructive pulmonary disease were copied by being smoked and lipopolysaccharide ,30 male SD rats of healthy clean grade were randomly divided into three groups:normal con-trol group,COPD model group and radix tetrastigmae group ,10 rats in each group.To observe the pathological chan-ges of lung tissue we used HE staining after the success of modeling , the expression of MMP-9 and TIMP-1 were measured in lung tissue ,bronchoalveolar lavage fluid and serum by ELISA ,the expression of MMP-9 and TIMP-1 in lung tissue was detected by immunohistochemistry .RESULTS The inflammation has been reduced in the groups of radix tetrastigmae group compared with the model group .ELISA results showed that the content of MMP-9 and TIMP-1 in the serum and bronchoalveolar lavage fluid of the model group lung tissue was higher than the control group ( P<0.05 ) ,MMP-9 and TIMP-1 content of radix tetrastigmae group compared with the model group decreased signifi -cantly ( P<0.05 ).Immunohistochemistry showed that ,compared with control group ,MMP-9 and TIMP-1 expression in the model of lung tissue was significantly increased ,the difference was statistically significant (P<0.05).Com-pared with model group ,MMP-9 and TIMP-1 expression in the lung tissue of radix tetrastigmae group was decreased , and the difference was statistically significant (P<0.05).CONCLUSION The water extract of radix tetrastigmae possibly through reduced MMP-9 , TIMP-1 expression , regulation of MMP-9/TIMP-1 imbalance , thereby intervention airway remodeling ,delaying disease progression ,which may be one of its mechanisms in COPD .