蓝莓益生菌通过影响IL-22/JAK1/STAT3信号通路改善非酒精性脂肪肝的研究

Study on effect of blueberry probiotics for improving non-alcoholic fatty liver disease by influencing IL-22/JAK1/STAT3 signaling pathway

目的研究蓝莓益生菌通过对白细胞介素-22(IL-22)调控的酪氨酸蛋白激酶-1(JAK1)/信号转导激活转录因子-3(STAT3)信号通路的影响,进一步探明其改善非酒精性脂肪肝病(NAFLD)的作用机制。方法清洁级SD大鼠40只分为正常对照组(NG)、观察组(MG)、蓝莓组(BG)、益生菌组(PG)和蓝莓+益生菌组(BPG)。除NG(100%普通饮食)外,其余大鼠均采用复合高脂饲料制备脂肪肝模型共12周。确认造模成功后再将剩余MG大鼠分为BG、PG及BPG,共观察8周。结果 BPG与MG、BG及PG比较:肝脏指数、血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)显著下降(P<0.01),高密度脂蛋白(HDL)显著升高(P<0.01);酶联免疫吸附试验(ELISA)检测IL-22:BPG的蛋白水平较MG、BG、PG增高(P<0.01);定量反转录酶-聚合酶链锁反应(qRT-PCR):BPG的JAK1、STAT3的表达较MG、BG、PG显著升高(P<0.01),胆固醇调节元件蛋白-1c(SREBP-1c)表达显著降低(P<0.01);Western blot:BPG的IL-22、JAK1、STAT3的表达较MG、BG、PG显著升高(P<0.01),SREBP-1c表达明显减少(P<0.01)。结论蓝莓益生菌能有效改善NAFLD的病理组织结构,减轻肝细胞脂肪变性,其机制可能是蓝莓益生菌可增加肝脏IL-22的表达,激活下游的JAK1/STAT 3信号通路,下调SREBP-1c的基因表达,抑制SREBP-1c的作用,增强胆固醇代谢,减少脂质沉积,是NAFLD的一个辅助治疗方案。

Objective To study the effect of blueberry probiotics on interlukin-22（IL-22）mediated Janus kinase-1（JAK1）/signal transducer and activator of transcription 3（STAT3）signaling pathway,and to further explore the potential mechanisms to improve non-alcoholic fatty liver disease（NAFLD）.Methods Forty clean grade rats were divided into the normal control group（NG）,model group（MG）,blueberry group（BG）,probiotics group（PG）and blueberry plus probiotics group（BPG）.Except for the NG group（100% general diet）,the fat liver model in the other groups was prepared by 12-week complex high fat diet.After the model establishment,the remained rats were divided into BG,PG and BPG groups for conducting 8-week observation.Results The liver index,alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,triglyceride（TG）,total cholesterol（TC）and low density lipoprotein（LDL）in the BPG group were significantly decreased compared with the MG,BG and PG groups（P〈0.01）and high density lipoprotein（HDL）was significantly increased（P〈0.01）;in IL-22 detected by the enzyme-linked immunosorbent assay（ELISA）：the protein level in the BPG group was significantly higher than that in the MG,BG and PG groups（P〈0.01）;in the quantificational reverse transcription-polymerase chain reaction（qRT-PCR）：the expressions of JAK1 and STAT3in the BPG group were significantly increased compared with the MG,BG and PG groups（P〈0.01）,while cholesterol regulatory element-binding protein-1c（SREBP-1c）expression in the BPG group was significantly decreased（P〈0.01）;in Western blot（WB）：the expressions of IL-22,JAK1 and STAT3in the BPG group were significantly higher than those in the MG,BG and PG groups,while the expression of SREBP-1cwas significantly declined（P〈0.01）.Conclusion Blueberry probiotics could effectively ameliorate the pathological tissue structure of NAFLD,attenuates hepatocyte steatosis,its mechanism may be that blueberry probiotics could increase expression of IL-22,activates the downstream signaling pathway of JAK1/STAT3,down-regulates the SREBP-1cgene expression and inhibits SREBP-1crole,enhances cholesterol metabolism,attenuates lipid deposit in liver,which may be an adjuvant scheme to treat NAFLD.