红景天苷对百草枯中毒大鼠肺组织MMP-2及TIMP-1表达的影响

Effects of salidroside on the expression of MMP-2 and TIMP-1 in paraquat poisoning pulmonary fibrosis rats

目的探讨红景天苷对百草枯中毒大鼠肺组织中基质金属蛋白酶-2(MMP-2)和组织特异性抑制因子-1(TIMP-1)表达的影响。方法将90只健康清洁级SD大鼠随机分为正常组10只、模型组40只、治疗组40只,后两组以染毒后不同时间又分为四个亚组,每亚组10只。模型组和治疗组制备急性百草枯中毒肺损伤模型,染毒后治疗组腹腔注射红景天苷10 mg/kg,模型组腹腔注射等量0.9%氯化钠溶液,每12小时一次。各组在1 h、6 h、24 h、72 h时间点取材。采用免疫组化法检测各组肺组织MMP-2、TIMP-1蛋白表达;Real-Time PCR法检测MMP-2 mRNA、TIMP mRNA表达。结果百草枯模型组和红景天苷治疗组MMP-2平均光密度值、TIMP-1平均光密度值、MMP-2mRNA表达均随着时间的延长逐渐升高(t分别=23.50、34.89、59.96、11.40、30.46、19.07;7.50、20.24、24.23、12.75、16.73、3.99;4.98、10.16、16.12、5.17、11.14、5.96;21.73、50.04、58.86、28.31、37.13、8.82;6.05、18.04、19.72、11.99、13.68;3.68、7.83、13.04、4.15、9.36、5.21,P均<0.05)。与对照组比较,百草枯模型组和红景天苷治疗组在6 h、24 h、72 h的MMP-2平均光密度值、TIMP-1平均光密度值、MMP-2 mRNA、TIMP-1 mRNA表达均明显升高(t分别=37.65、67.01、55.06;24.94、53.76、42.60;9.11、25.94、23.67;5.93、19.63、16.48;15.22、12.94、13.98;9.98、9.62、17.70;15.26、7.74、8.17;13.10、4.32、5.06,P均<0.05)。与百草枯模型组比较,红景天苷治疗组在6 h、24 h、72 h的MMP-2平均光密度值、TIMP-1平均光密度值、MMP-2 mRNA、TIMP-1 mRNA均明显降低(t分别=12.71、13.25、12.46;3.18、6.31、7.20;5.24、4.36、4.37;2.16、3.42、3.11,P均<0.05)。结论红景天苷通过降低MMP-2、TIMP-1及其mRNA的表达,保护百草枯中毒大鼠肺组织。

Objective To explore the effect of salidroside（SDS） on the expression of matrix metalloproteinase-2（MMP-2） and the tissue inhibitor of metalloproteinase-1（TIMP-1） in paraquat poisoning pulmonary fibrosis rats. Methods Ninety Sprague-Dawley rats （sanitary degree） were randomly divided into normal group （n=10）, model group （n=40） and SDS treatment group（n=40）. The model group and SDS treatment group were randomly divided into four subgroups with 10 cas-es each according to different time points of sacrifice. And then the model group and SDS treatment group made the lung injury model induced by PQ poisoning at 1 hour, 6 hours, 24 hours and 72 hours respectively. After the poisoning, SDS group was given SDS, 10mg/kg, per 12 hours while the model group was given normal saline solution with the same vol-ume until sacrifice. The immunohistochemistry was used to determine the expressions of MMP-2 protein and TIMP protein. The levels of MMP-2 mRNA and TIMP mRNA were examined by real-time PCR. Results The expression of MMP-2,＆amp;nbsp;TIMP-1 and MMP-2mRNA in PQ model group and SDS treatment group were gradually increased with the time prolonged （t=23.50, 34.89, 59.96, 11.40, 30.46, 19.07; 7.50, 20.24, 24.23, 12.75, 16.73, 3.99; 4.98, 10.16, 16.12, 5.17, 11.14, 5.96;21.73, 50.04, 58.86, 28.31, 37.13, 8.82; 6.05,18.04, 19.72, 11.99, 13.68;3.68, 7.83, 13.04, 4.15, 9.36, 5.21, P〈0.05）. Compared to control group, the expression of MMP-2,TIMP-1, MMP-2 mRNA and TIMP-1 mRNA in PQ model group and SDS treatment group at 6 hours,24 hours and 72 hours were significantly increased （t=37.65, 67.01, 55.06; 24.94, 53.76, 42.60; 9.11, 25.94, 23.67; 5.93, 19.63, 16.48; 15.22, 12.94, 13.98; 9.98, 9.62, 17.70; 15.26, 7.74, 8.17; 13.10, 4.32, 5.06, P〈0.05）. Compared to PQ model group, the expression of MMP-2,TIMP-1, MMP-2 mRNA and TIMP-1 mRNA in SDS treatment group at 6 hours, 24 hours and 72 hours were significantly decreased （t=12.71, 13.25, 12.46; 3.18, 6.31, 7.20; 5.24, 4.36, 4.37; 2.16, 3.42, 3.11, P〈0.05）. Conclusions SDS can regulate the expression of MMP-2 and TIMP-1 to protect the lung tissue injured by PQ poisoning.