VLDL与肝脂肪变性的关系及LXRα对VLDL代谢的调控

综述了肝脏X受体亚基LXRα对极低密度脂蛋向(VLDL)调控的机理及VLDL对肝脂肪变性的影响。     

铅与维生素C对小鼠肝脏脂质过氧化的影响

以五周龄昆白系小鼠为试验动物,在饲喂小鼠普通日粮基础上每天灌喂一定量铅(Pb)、维生素C(Vc)、Vc Pb,Vc用量200mg/kg,Pb四个浓度分别为1.2g/L、0.4g/L、0.13g/L、0.043g/L,饲喂期三周,检测小鼠肝脏中铅与丙二醛(MDA)含量以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、过氧化物酶(POD)的活性变化。结果表明:铅在小鼠肝脏中大量蓄集,并引起MDA含量增加;加Pb组与空白对照组相比SOD酶活性降低,且随着铅浓度的降低而升高;CAT活性测定显示:Pb1、Pb2组与空白对照组相比差异显著(p<0.05),Pb3组差异极显著(p<0.01),除Vc Pb4组与Pb4组相比差异不显著(P>0.05)外,其他Vc Pb组与其对应加Pb组比较,均差异显著(p<0.05);POD活性测定表明:Vc组与空白组相比差异极显著(p<0.01),Pb1、Pb3组与空白组比较差异显著(p<0.05),Pb2、Pb4与空白组比较差异极显著(p<0.01),除Vc Pb1组与Pb1组差异不显著(P>0.05),其他Vc加Pb组与单独加Pb组相比差异极显著(p<0.01)。因此,Pb可增强小鼠肝脏脂质过氧化,而Vc可减轻铅引起的过氧化损伤。     

T0901317 induces apoptosis of human breast cancer MDA-MB-231 cells by up-regulating LXRα expression

AIM: To investigate the pro-apoptotic effect of T0901317, an artificial agonist of liver X receptor α (LXRα), on human breast cancer MDA-MB-231 cells and its mechanism. METHODS: MDA-MB-231 cells were treated with different concentrations (0, 10, 20 and 40 μmol/L) of T0901317 for different time (0, 12, 24 and 48 h). The cell apoptosis was determined by Annexin V/propidium iodide staining and Hoechst 33342 staining. The expression of apoptosis-related proteins, such as Bcl-2, caspase 3 and cleaved caspase-3, and LXRα was determined by Western blot. The mRNA expression of Bcl-2 and LXRα was analyzed by RT-qPCR. RESULTS: T0901317 induced the cell apoptosis in a dose-and time- dependent manner. The expression of cleaved caspase-3 and LXRα was up-regulated, but Bcl-2 was down-regulated by T0901317. The mRNA expression of Bcl-2 was down-regulated, while LXRα was up-regulated by T0901317.CONCLUSION: T0901317 up-regulates LXRα expression and induces the apoptosis of MDA-MB-231 cells.     

Presumptive Iatrogenic Microcystin‐Associated Liver Failure and Encephalopathy in a Holsteiner Gelding

An 8‐year‐old Holsteiner gelding was presented for evaluation of anorexia, obtundation, icterus, and mild colic signs of 48 hours duration. History, physical examination, and initial diagnostics were suggestive of hepatic disease and encephalopathy. Microcystin toxicosis was suspected based on historical administration of a cyanobacteria supplement, associated serum biochemistry abnormalities, and characteristic histopathological changes. Microcystin contamination was confirmed in both supplement containers fed to the horse. Fulminant hepatic failure and encephalopathy progressed resulting in euthanasia. Necropsy findings were consistent with microcystin induced liver failure.     

Incidence,Timing, and Risk Factors of Azathioprine Hepatotoxicosis in Dogs

Background

The use of azathioprine (AZA) in dogs is limited by the development of hepatotoxicosis and cytopenias.

Hypothesis and Objectives

To characterize the observed incidence, timing, and risk factors for AZA hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias.

Animals

Fifty‐two dogs treated with AZA with clinical and biochemical follow‐up, with a subset of 34 dogs available for determination of changes in liver enzyme activities in serum.

Methods

Retrospective medical record review, from January 2009 through December 2013.

Results

Hepatotoxicosis (as defined by a >2‐fold increase in serum ALT) was observed in 5 of 34 dogs (15%) within a median onset of 14 days (range, 13–22 days). Dogs had a median 9‐fold increase in ALT and 8‐fold increase in ALP, which stabilized or resolved with drug discontinuation or dose reduction. German shepherds were significantly over‐represented (3 of 5 dogs with hepatotoxicosis; P = .0017). Thrombocytopenia or neutropenia were seen in 4 of 48 dogs with CBC follow‐up (8% of dogs), but occurred significantly later in treatment (median onset, 53 days; range 45–196 days) compared to hepatotoxicosis (P = .016).

Conclusions and Clinical Importance

These results support the routine monitoring of liver enzymes during the first 1–4 weeks of AZA treatment in dogs, with continued monitoring of the CBC. Additional studies are warranted to characterize the apparently higher risk of AZA hepatotoxicosis in German shepherds.     

鹅终止填饲后肝脏的生理性恢复试验

鹅短期强制填饲形成肥肝后,终止填饲观察肝脏生理性恢复情况。终填15 d、30 d后,体重和肝脏重快速恢复,接近正常;血液中TBA、TG等变化规律不明显,CHO终填30 d恢复,TP、ALB、GLO等体症蛋白含量变化不显著,ALT、AST、LDH、CHE等酶类填饲后大幅上升,终填后迅速回复,其中AST填后含量达191.8 U.L-1,升高2.87倍,终填15 d、30 d回复到正常的106.67%和84.44%;肝细胞内脂肪空泡迅速减少,终填30 d基本消失,向正常肝细胞过渡。试验结果表明肥肝生产是正常可逆的生理过程,通过自然放养,可基本回复到正常状态。     

Functional analysis of differential microRNA expression profile in mouse fibrotic liver tissues induced by CCl4

AIM:To discover the expression profile of microRNAs (miRNAs) in mouse fibrotic liver tissues induced by carbon tetrachloride (CCl4), and to investigate the functions of these differential miRNAs based on the gene ontology (GO) analysis and KEGG Pathway analysis. METHODS:The mice were randomly divided into normal group and model group. Liver fibrosis was induced by subcutaneous injection of CCl4. miRNA expression profile of the liver tissues was assayed by a mouse miRNA microarray (Agilent 12.0). The differential expression of miRNAs between the normal and model mice was screened, and GO analysis and KEGG Pathway analysis were performed to determine the functions of these differential miRNAs. RESULTS:Thirty-nine miRNAs with differential expression were discovered in the model mice compared with the normal mice, among which 23 were up-regulated and 16 were down-regulated. GO analysis and KEGG Pathway analysis indicated that most pathological processes of liver fibrosis regulated by miRNAs included cell proliferation and activation, cell apoptosis, cell cycle, cell adhesion, inflammatory reaction, cell migration, transforming growth factor β (TGF-β) signaling pathway, Wnt signaling pathway and proteometabolism process. GO analysis revealed that the key up-regulated miRNAs were mmu-miR-322, mmu-miR-15b, mmu-miR-195, mmu-miR-200b and mmu-miR-214, and the key down-regulated miRNAs were mmu-miR-16, mmu-miR-130a, mmu-miR-101b, mmu-miR-30a and mmu-miR-30e. Analyzing the target genes screened out by GO analysis and Pathway analysis simultaneously, we found that the key up-regulated miRNAs included mmu-miR-200b, mmu-miR-322, mmu-miR-106b, mmu-miR-23a and mmu-miR-15b, and the key down-regulated miRNAs included mmu-miR-16, mmu-miR-30e, mmu-miR-30c, mmu-miR-30a and mmu-miR-130a. CONCLUSION: Differential expression of miRNAs is discovered in mouse fibrotic liver tissues induced by CCl4 compared with the normal liver tissues. Most of the pathological processes involved in liver fibrosis may be regulated by miRNA, such as cell proliferation and activation, cell adhesion and apoptosis, cell migration and differentiation, metabolism, TGF-β receptor signaling pathway and so on.