过氧化物酶增殖物激活受体γ抑制肝脏缺血再灌注损伤中Toll样受体4表达的意义

Significance of PPARγ Inhibiting TLR4 Expression in Mice Partial Hepatic Ischemia/reperfusion

目的研究肝部分缺血再灌注损伤过程中过氧化物酶增殖物激活受体γ(PPARγ)、Toll样受体4(TLR4)和IL-10相互作用的可能机制。方法制作小鼠肝脏部分缺血再灌注损伤模型。30只小鼠随机分为4组:罗格列酮组、罗格列酮+双酚丙控二环氧甘油醚(BADGE)组、BADGE组、对照组。复灌4h取材。采用实时荧光PCR方法检测PPARγ、TLR4在小鼠肝脏部分缺血再灌注损伤中的表达,同时检测血清TNF、IL-10、ALT水平。结果罗格列酮组较其它三组PPARγ的表达和血清IL-10水平增高,TLR4的表达、血清TNF-α和ALT水平较其它三组减弱(P<0.05),罗格列酮+BADGE组、BADGE组及对照组间的PPARγ和TLR4表达无显著差别。结论在鼠肝脏缺血再灌注过程中,罗格列酮激活PPARγ并上调IL-10水平,抑制TLR4表达。

Objective To investigate the interactive specific mechanism and biological effect among PPARγ, TLR4 and IL- 10 and find the potential therapeutic,targets during the process of hepatic partial ischemia/reperfusion injury （IRI）. Methods The model of mouse partial live IRI was established. All the rats were randomly divided into 5 groups： the rosiglitazone group,rosiglitazone ＋ BADGE group, BADGE group, DMSO group and sham group. The liver samples were collected at the fourth hour of reperfusion. PPARγ and TLR4 mRNA was detected quanti- tatively by real - time RT - PCR. The level of serum TNF -α, IL - 10 and ALT in portal vein was measured. Results The expression of PPARγ mRNA and level of IL - 10 in portal vein in rosiglitazone group significantly increased, while the expression of TLR4 mRNA, the level of TNF -α and ALT in rosiglitazone group decreased during the process of hepatic partial IRI （P 〈0.05）. Conclusions These results demonstrate that rosiglitazone through a PPARγ-dependent path- way markedly may depress the expression of TLR4 and TLR4 mediating inherent immune response, finally lessen hepatocellular damage.