罗格列酮对小鼠日本血吸虫病肝纤维化基质金属蛋白酶-2的影响

Effects of rosiglitazone on matrix metalloproteinase-2 in mice with schistosomiasis and liver fibrosis

目的:研究PPARγ配体罗格列酮治疗小鼠血吸虫病肝纤维化,血清MMP-2与TIMP-2的变化及肝组织MMP-2与TIMP-2的基因表达方法:昆明小鼠50只,随机分为正常对照组A、感染对照组B、吡喹酮治疗组C、罗格列酮治疗组D及罗格列酮加吡喹酮治疗组E.除正常对照组外,其余各组均建立血吸虫病肝纤维化小鼠模型.用ELISA法检测血清MMP-2及TIMP-2的含量,实时荧光定量PCR反应观察小鼠肝组织MMP-2 mRNA及TIMP-2 mRNA的表达.结果:D,E组血清MMP-2的含量(306.0±62.3μg/L,312.0±54.3μg/L)及肝组织MMP-2 mRNA的表达[-19.1±(-6.0),-20.4±(-6.2)]高于A组[221.3±39.2μg/L,-26.3±(-5.3):P<0.051,但明显低于B组[411.3±57.5μg/L,-12.2±(-4.4),P<0.05]和C组[402.9±57.2μg/ L,-12.8±(-4.0),P<0.051.B,C,D和E组血清TIMP-2的含量及肝组织TIMP-2 mRNA的表达均显著高于正常对照组[209.3±60.5μg/L,-20.5±(-4.7);213.5±66.0μg/L,-19.9±(-5.1);223.6±65.3μg/L,-18.8±(-5.5);224.5±64.4μg/L,-19.7±(-4.3) vs 150.4±46.5μg/L,-27.2±(-6.0),P<0.05],但这4组间TIMP-2值无显著性差异(P>0.05).结论:MMP-2在血吸虫病肝纤维化形成中起促进作用,PPARγ配体罗格列酮的抗肝纤维化机制与其下调MMP-2的表达有一定关系.

AIM： To study the effects of rosiglitazone, a peroxisome proliferator-activator receptor （gamma） ligand, on serum levels of matrix metalloproteinase-2 （MMP-2） and the tissue inhibitor of metalloproteinase-2 （TIMP-2）, along with the hepatic expression of MMP-2 and TIMP-2 mRNA in mice with liver fibrosis caused by Schistosoma japonicum infection. METHODS： Fifty mice were divided into five groups： one uninfected group （A）, and four schistosomiasis groups （B-E）： without any treatment （B）, praziquantel treatment （C）, rosiglitazone treatment （D）, and rosiglitazone and praziquantel treatment （E）. Serum levels of MMP-2 and TIMP-2 were measured by ELISA. Hepatic expression of MMP-2 and TIMP-2 mRNA were determined by real-time quantitative PCR. RESULTS： Serum level and hepatic mRNA expression of MMP-2 were markedly higher in groups D and E [306.0 ± 62.3 μg/L, 3120 ± 54.3 μg/L; -19.123 ± （-5.965）, -20.375 ± （-6.189）] than in group A [221.3 ± 39.2 μg/L, -26.324 ± （- 5.314）; P 〈 0.05], but were lower than in group B [411.3 ± 57.5 μg/L, -12.227 ± （-4.426）, P 〈 0.05] and group C [402.9 ± 57.2 μg/L, -12.804 ± （- 4.036）, P 〈 0.05]. Serum level and hepatic mRNA expression of TIMP-2 was markedly increased in the four schistosomiasis groups compared to the normal group [209.3 ± 60.5μg/L, -20.516 ± （-4.716）; 213.5 ± 66.0μg/L, -19.944 ± （-5.052）; 223.6 ± 65.3 μg/L, -18.767 ± （-5.509）; 224.5 ± 64.4 μg/L, -19.676 ± （-4.320） vs 150.4 ± 46.5 μg/L, - 27.186 ± （-5.985）, P 〈 0.05]; however, there was no significant difference among the schistosomiasis groups （P 〉 0.05）. CONCLUSION： MMP-2 plays a role in promoting liver fibrosis. Rosiglitazone can relieve liver fibrosis because it down-regulates the expression of MMP-2 in mice with schistosomiasis and liver fibrosis.