多房棘球蚴感染对小鼠肝脂质代谢的影响

The Effect of Echinococcus multilocularis Infection on Lipid Metabolism in the Liver of Mice

旨在探讨多房棘球蚴感染早期对小鼠肝脂质代谢的影响。选取60只清洁级BALB/c小鼠(6周龄,雄性)随机分为试验组和对照组,每组30只。试验组小鼠每只腹腔接种600个原头蚴,对照组小鼠腹腔注射等体积的PBS缓冲液。采用原位两步循环灌流及多步低速差速离心分离纯化肝实质细胞。利用高通量测序分析感染3月小鼠肝实质细胞差异表达的mRNA,并对其进行KEGG、GO分析和qRT-PCR验证。制备多房棘球蚴感染2、3和6月小鼠的肝组织切片,分别进行油红O染色,并通过qRT-PCR检测多房棘球蚴感染不同感染时期肝实质细胞脂质代谢相关基因的表达水平。结果表明,与未感染对照组相比,小鼠感染多房棘球蚴后3、6月肝脂肪沉积明显增多;感染2月的肝实质细胞脂质合成相关基因Scd1、Fasn和Srebf1,以及脂质氧化分解相关基因Acox1和Cpt1α均明显上调;感染3月的肝实质细胞Scd1、Fasn、Srebf1及Cd36的表达水平均明显升高,而Acox1、Cpt1α、Pparγ和Pparα的表达水平明显降低。上述结果表明,多房棘球蚴感染早期可能通过促进肝实质细胞的脂质合成,抑制脂质氧化分解,从而导致肝脂质沉积。

To investigate the effect of Echinococcus multilocularis infection on the lipid metabolism in the liver of mice, 60 clean-grade BALB/c mice(6-week-old, male) were randomly divided into two groups with 30 mice in each group. The mice in the experimental group were intraperitoneally injected with 600 protoscoleces, while mice in the control group were treated with an equal volume of PBS. Hepatocytes were obtained by separation and purification. High-throughput sequencing was used to analyze the differentially expressed mRNAs of hepatocytes from mice liver at 3 months post infection(Mpi) and KEGG,GO analysis and qRT-PCR were used for verification. Liver tissue sections of mice at 2, 3 and 6 Mpi were stained with Oil Red O. The expression levels of lipid metabolism-related genes in hepatocytes at different infection stages were detected by qRT-PCR. The results showed that the fat deposition in the liver increased significantly compared with the control group at 3 and 6 Mpi. Lipid synthesis-related genes Scd1, Fasn and Srebf1, and lipid oxidation-related genes Acox1 and Cpt1α were significantly up-regulated in hepatocytes at 2 Mpi of E. multilocularis;the expression levels of Scd1, Fasn, Srebf1 and Cd36 were significantly increased, however, expression levels of Acox1, Cpt1α, Pparγ, and Pparα were significantly decreased in hepatocytes at 3 Mpi of E. multilocularis. The above results suggest that E. multilocularis infection may induce hepatic lipid deposition by promoting lipid synthesis in hepatocytes and inhibiting lipid oxidative.