清热燥湿方对急性肺损伤大鼠肺组织基质金属蛋白酶2及其抑制因子基因表达的影响

目的探讨清热燥湿方对细菌脂多糖(LPS)诱导急性肺损伤(ALI)大鼠肺组织基质金属蛋白酶2(MMP-2)及其抑制因子(TIMP-2)基因表达的影响。方法 40只雄性Wistar大鼠随机分为正常对照组、LPS模型组、地塞米松组和清热燥湿方组,每组再分为4h和8h两个亚组。分别用地塞米松和清热燥湿方在LPS诱导ALI模型前预处理大鼠,分别采用免疫组化法和实时荧光定量PCR法检测大鼠肺组织MMP-2及TIMP-2 mRNA表达。结果与模型组相比,4h清热燥湿方组MMP-2 mRNA表达明显降低(P0.01),TIMP-2蛋白染色阳性面积率及TIMP-2 mRNA表达均显著增高(P0.01或P0.05);8h清热燥湿方组MMP-2蛋白染色阳性面积率及MMP-2 mRNA表达显著降低(P0.01或P0.05)。病理学观察显示,模型组大鼠肺组织出现大片出血及坏死,清热燥湿方组大鼠肺组织病理损伤程度较模型组减轻。结论清热燥湿方能减轻LPS致ALI大鼠肺组织损伤,对LPS致ALI大鼠有保护作用。

Effects of Qingrezaoshi Decoction on the Expression of MMP-2, TIMP-2 and Their mRNA in ALI Rats Caused by LPS

Objective To investigate the effects of Qingrezaoshi decoction on the expression of MMP-2 andtheir mRNA （MMP-2 mRNA）, tissue inhibitor of MMP-2 and its mRNA （TIMP-2 mRNA） in the rats with acutelung injury （ALI） caused by LPS. Methods Forty male Wistar rats were randomly divided into 4 groups：normal control group, LPS model group, dexamethasone group and Qingrezaoshi decoction group. Eachgroup had two subgroups, 4 h and 8 h after LPS injection. All rats, except normal control group, wereadministrated with LPS by intravenous injection to induce ALI. The rats in dexamethasone group andQingrezaoshi decoction group were treated by dexamethasone （oral） and Qingrezaoshi decoction （oral）respectively before LPS-induced ALI. The expression of MMP-2 and TIMP-2 were measured byimmunohistochemistry ABC, and their mRNAs were measured by real-time fluorescent PCR, while thehistopathology of the lung injury was observed by light microscope. Results In 4 h Qingrezaoshi decoctiongroup, the expression of MMP-2 mRNA was significantly decreased while the expression of TIMP-2 proteinand its mRNA were significantly increased compared with model group （P 〈0.01 or P 〈0.05）. In 8 hQingrezaoshi decoction group, the expression of MMP-2 protein and its mRNA were significantly decreased（P 〈0.01 or P 〈0.05）. Pathological observation showed that pulmonary hemorrhage and necrosis werelargely seen in model group and a better condition in Qingrezaoshi decoction group. ConclusionQingrezaoshi decoction may abate the histopathology of the lung injury and it has protective effects onendotoxin-induced ALI in rats.