益生菌L.Casei hang对大鼠急性肝损伤的保护作用及其对TLR4-ERK-PPAR-γ通路的影响  

Protective effects of probiotic Lactobacillus Casei Zhang against acute liver injury in rats and its effect on the TLR4-ERK-PPAR-γ signaling pathway

作　　者：谢基明 王玉珍[2] 张威[2] 云小乐[2] 巩培[2] 刘竟然[2] 赵世敏[2] 康鸿斌[3] 张和平[4] 

机构地区：[1]内蒙古自治区人民医院检验科,呼和浩特010010 [2]内蒙古农业大学生命科学学院,呼和浩特010018 [3]内蒙古医科大学第一附属医院,呼和浩特010050 [4]内蒙古农业大学教育部乳品生物技术与工程重点实验室,呼和浩特010018

出　　处：《中国免疫学杂志》2013年第9期910-913,922,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金(31270922;81260622;81360394);中国博士后基金(20110491553);内蒙古自然科学基金(2010MS0513;2011MS1112;2012 MS1156);内蒙古科技厅应用技术研发计划项目(20070501)

摘　　要：目的:研究益生菌L.Casei Zhang(LCZ)对大鼠急性肝损伤的保护作用并探讨相关机制。方法:48只Wistar大鼠随机分为4组:对照组、模型组、益生菌组和地塞米松组。采用腹腔注射脂多糖(LPS)和D-氨基半乳糖(D-GalN)建立大鼠急性肝损伤模型。益生菌组在造模前连续30天灌服LCZ(1×109CFU)。地塞米松组在造模前腹腔注射地塞米松(10 mg/kg)。造模后16小时处死大鼠,检测血清中ALT和AST的变化、检测肝脏匀浆中TNF-α和NO的表达。采用免疫组化方法检测肝脏组织中TLR4和p-ERK的表达水平;采用RT-PCR和Western blot方法检测肝脏中PPAR-γ表达的变化。结果:益生菌组和地塞米松组血清ALT、AST以及肝脏中TNF-α和NO表达显著低于模型组。同时,组织切片显示,肝细胞坏死程度也显著减轻。免疫组化结果显示,与模型组相比,益生菌组和地塞米松组肝脏中TLR4和p-ERK水平也显著降低。PPAR-γ表达在模型组中显著降低,在益生菌组和地塞米松组表达又有所恢复。结论:益生菌L.Casei Zhang对LPS/D-GalN诱导的大鼠急性肝损伤有保护作用,该作用与抑制TLR4-ERK通路以及上调PPAR-γ的表达有关。Objective：To study the protective effects of probiotic L. Casei Zhang （LCZ） on acute liver injury and examine the underling mechanisms. Methods ： Forty-eight Wistar rats were randomly divided into 4 groups ： control group, model group, the probiotics group and the dexamethasone group. A rat model of acute liver injury was established by intraperitoneally injection of lipopolysaccharide （LPS） and D-galactosamine （D-GalN）. Rats were administrated with LCZ （ 1 × 10^9CFU） for 30 consecutive days by oral garage prior to model establishing. The dexamethasone group was intraperitoneally injected with dexamethasone （ 10 mg/kg） before LPS/ D-GaIN challenge. The rats were sacrificed 16 h after LPS/D-GalN challenge. ALT and AST levels in serum and the production of TNF-α and NO in liver homogenates were measured. The expression of TLR4 and phosphorylation of ERK in liver tissue were detected by immunohistochemical assays. The expression of PPAR-γ in the liver was examined by RT-PCR and Western blot. Results： The ALT and AST levels and the production of liver TNF-α and NO were significantly lower in the probiotics group and dexamethasone group than that of the model group. Meanwhile, the biopsy revealed reduced necrosis of liver cells. Immunohistochemical results showed that the hepatic TLR4 and p-ERK expression in the probiotic group and dexamethasone group was also significantly reduced compared with the model group. PPAR-γ expression in the model group was significantly reduced. However, the expression of PPAR-γrecovered in the probiotics group and dexamethasone group. Conclusion： The hepatoprotective effects of LCZ against LPS/D-GalN-induced acute liver injury in rats are associated with an inhibition of TLR4-ERK signaling pathway and an up-regulation of PPAR-γexpression.

关 键 词：益生菌 肝损伤 TLR4 P-ERK PPAR-Γ 

分 类 号：R392.11[医药卫生—免疫学]