骨髓间充质干细胞对急性出血坏死性胰腺炎大鼠肺组织Toll样受体2/4mRNA表达的影响及意义

Effect of bone mesenchymal stem cells on toll-like receptor 2/4 expression in lungs of rats with acute hemorrhagic necrotizing pancreatitis

目的 研究骨髓间充质干细胞（BMSCs）对急性出血坏死性胰腺炎（AHNP）大鼠肺组织T0ll样受体（TLR）2/4表达的影响并初步探讨其机制.方法 采用逆行胰胆管牛磺胆酸钠注射制造AHNP大鼠模型,动物分为假手术组、胰腺炎组和BMSCs治疗组;流式细胞仪检测BMSCs表面标记阳性细胞率;RT-PCR方法检测肺组织TLR2/4mRNA表达变化;同时观察肺组织形态学改变,进行肺湿/干重比（W/D）测定.结果 与假手术组比较,胰腺炎组大鼠从3h时肺组织TLR2/4mRNA表达开始增高,在12 h时肺组织TLR2/4mRNA表达达到峰值;同时肺损伤加重,肺组织TNF-α浓度升高（P＜0.05）.给予BMSCs治疗后,TLR2/4mRNA表达降低,肺损伤程度减轻,肺组织TNF-α浓度降低（P＜0.05）.结论 急性出血坏死性胰腺炎时,组织内TLR2和TLR4mRNA表达上调,肺组织损伤加重.BMSCs可以明显抑制AHNP肺组织TLR2/4mRNA的表达,降低肺组织TNF-α浓度,从而减轻肺损伤.

Objective To investigate the effect of bone mesenchymal stem cells on Toll-like receptors （TLR） 2/4 expression in the lungs of rats with acute hemorrhagic necrotizing pancreatitis （AHNP）. Methods Seventy SD male rats were randomly divided into sham-operation group （n=10）, AHNP group（n=30） and MSCs-treated group（n=30）. Masc rate of BMSCs with surface mark were measured by flow cytometer. TLR2/4mRNA expression in the the lung were measured by RT-PCR, and The ratio of Wet/dry and lung histological changs were observed. Results TLR2/4 mRNA could be detected in the lungs with low values in sham-operation group, markedly increased in 3 h, and peaked in 12 h in AHNP group （P〈0.05）. Lung injuries were aggravated and the levels of TNF-α in the lung were increased （P〈0. 05） . Treatment with MSCs could effectively inhibit TLR2/4 mRNA expression and relieve lung injuries. The levels of TNF-α in the lung were decreased （P〈0.05）. Conclusions The expression of TLR2/4 mRNA is increased in the lungs in AHNP and the lung injuries are aggravated. MSCs could markedly inhibit TLR2/4 mRNA expression in the lungs in AHNP, which would lead to relief of lung injury.