Sun S S, Wu Y X, Cheng M L, Chen C W, Peng Y S, Miao Q, Bian Z L, Wang X J, Fu Q C
The 405th Hospital of PLA, Liver Disease Research Center, Shanghai 200235, China; Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Lishui Central Hospital, Zhejiang 323000, China.
Zhonghua Gan Zang Bing Za Zhi. 2019 Jan 20;27(1):45-50. doi: 10.3760/cma.j.issn.1007-3418.2019.01.010.
To probe into the mechanism and interventional effects of silybin-phospholipid complex on amiodarone-induced steatosis in mice. Eight-week-old male C57BL/6 mice were divided into three groups (5 mice in each group): a control group (WT) with normal diet, a model group with amiodarone 150mg/kg/d by oral gavage (AM), and an intervention group on amiodarone 150mg/kg/d combined with silybin-phospholipid complex(AM+SILIPHOS. All mice were fed their assigned diet for one week. Then, one week later, serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol and high-density lipoprotein were detected of each group. A liver pathological change was observed by oil red O and H&E staining. Ultrastructural pathological changes of hepatocytes were observed to evaluate the intervention effect by transmission electron microscopy. RT-q PCR was used to detect the expression of peroxisome proliferator-activated receptor alpha and its regulated lipid metabolism genes CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 in liver tissues. Intra-group comparison was done by paired t-test. One-way ANOVA was used for comparison between groups and semi-quantitative data were tested using Mann-Whitney U test. Oil Red O and H&E staining results of liver tissue in the intervention group showed that intrahepatic steatosis was significantly reduced when compared to model group. Transmission electron microscopy showed that the model group had pyknotic nuclei, mitochondrial swelling, structural damage, and lysosomal degradation whereas the intervention group had hepatic nucleus without pyknosis, reduced mitochondrial swelling and slight structural damage than that of model group. RT-q PCR results showed that the expression of peroxisome proliferator-activated receptor alpha, CPTI, CPTII, Acot1, Acot2, ACOX, Cyp4a10 and Cyp4a14 were increased in the model group but the expression of CPTI, Cyp4a14, Acot1 and peroxisome proliferator-activated receptor alpha were decreased in the intervention group ( < 0.05). Silybin-phospholipid complex can alleviate amiodarone-induced steatosis, and its mechanism may play a role in protecting mitochondrial function and regulating fatty acid metabolism. Thus, silybin-phospholipid complex has potential intervention effect on amiodarone-induced fatty liver.
探讨水飞蓟宾磷脂复合物对胺碘酮诱导的小鼠脂肪变性的作用机制及干预效果。将8周龄雄性C57BL/6小鼠分为三组（每组5只）：正常饮食的对照组（WT）、经口灌胃给予胺碘酮150mg/kg/d的模型组（AM）、以及给予胺碘酮150mg/kg/d联合水飞蓟宾磷脂复合物的干预组（AM+SILIPHOS）。所有小鼠按指定饮食喂养1周。然后，1周后，检测每组小鼠血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、甘油三酯、总胆固醇和高密度脂蛋白。通过油红O和苏木精-伊红染色观察肝脏病理变化。通过透射电子显微镜观察肝细胞超微结构病理变化以评估干预效果。采用RT-q PCR检测肝脏组织中过氧化物酶体增殖物激活受体α及其调控的脂质代谢基因CPTI、CPTII、Acot1、Acot2、ACOX、Cyp4a10和Cyp4a14的表达。组内比较采用配对t检验。采用单因素方差分析进行组间比较，半定量数据采用Mann-Whitney U检验。干预组肝脏组织油红O和苏木精-伊红染色结果显示，与模型组相比，肝内脂肪变性明显减轻。透射电子显微镜显示，模型组细胞核固缩、线粒体肿胀、结构破坏、溶酶体降解，而干预组肝细胞核无固缩，线粒体肿胀减轻，结构破坏较模型组轻微。RT-q PCR结果显示，模型组过氧化物酶体增殖物激活受体α、CPTI、CPTII、Acot1、Acot2、ACOX、Cyp4a10和Cyp4a14表达增加，而干预组CPTI、Cyp4a14、Acot1和过氧化物酶体增殖物激活受体α表达降低（P<0.05）。水飞蓟宾磷脂复合物可减轻胺碘酮诱导的脂肪变性，其机制可能在保护线粒体功能和调节脂肪酸代谢中发挥作用。因此，水飞蓟宾磷脂复合物对胺碘酮诱导的脂肪肝具有潜在干预作用。
Zotero 插件