解毒化瘀颗粒对肝衰竭大鼠的作用机制——肝损伤和肝线粒体自噬蛋白Mfn1、Mfn2的影响

The mechanism of action of Jiedu Huayu Granules on liver failure rats——The effects of liver injury and liver mitochondrial autophagy proteins Mfn1 and Mfn2

研究解毒化瘀颗粒对肝衰竭大鼠肝损害和线粒体自噬特异性蛋白Mfn1、Mfn2表达的作用。将180只SPF级Wistar大鼠随机分为正常组、模型组和解毒化瘀颗粒给药组(JDHYKL组)。采用D-GalN+LPS复制急性肝衰竭大鼠模型。JDHYKL组给予解毒化瘀颗粒造模前5天开始灌胃给药,延续至成模后24 h,正常组与模型对照组分别给予等量蒸馏水代替。检测各组大鼠ALT,AST和TBIL水平;HE染色观察各组大鼠肝组织病理变化;蛋白免疫印迹法(Western blot)检测线粒体自噬特异性蛋白Mfn1、Mfn2表达。经解毒化瘀颗粒治疗后大鼠肝组织肝细胞形态组织结构基本正常,细胞呈条索状排列,部分假小叶形成,肝细胞坏死及空泡化较模型组减轻,同时可明显降低LF大鼠ALT、AST(P<0.05),提高Mfn1、Mfn2表达(P<0.05)。解毒化瘀颗粒可能是通过上调Mfn1和Mfn2的表达抑制线粒体分裂,推动线粒体结合,降低碎片化现象,保护线粒体,而对大鼠肝衰竭发挥保护作用。

This study examines the effect of Jiedu Huayu Granules on liver damage and expression of mitochondrial autophagy-specific proteins Mfn1 and Mfn2 in liver failure rats.180 SPF Wistar rats were randomly divided into normal group,model group and Jieduhuayu granule administration group(JDHYKL group).D-GalN+LPS was used to replicate the rat model of acute liver failure.In the JDHYKL group,Jiedu Huayu granules were given by intragastric administration 5 days before modeling,and continued until 24 hours after modeling.The normal group and the model control group were given the same amount of distilled water instead.The levels of ALT,AST and TBIL were detected in each group;HE staining was used to observe the pathological changes of liver tissue in each group;Western blot was used to detect the expression of mitochondrial autophagy-specific proteins Mfn1 and Mfn2.After treatment with Jiedu Huayu Granules,the morphology and structure of liver cells in rat liver tissues were basically normal.The cells were arranged in the form of cords and some pseudolobules were formed.Hepatocyte necrosis and vacuolization were reduced compared with the model group.ALT,AST(P<0.05)of LF rats were significantly reduced,and Mfn1,Mfn2 expression(P<0.05)increased.Jiedu Huayu Granules may inhibit mitochondrial division by increasing the expression of Mfn1 and Mfn2,promote mitochondrial binding,reduce fragmentation,protect mitochondria,and thus play a protective role in rat liver failure.