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ObjectiveTo explore the mechanism of Broussonetiae Fructus （BF） in preventing and treating drug-induced liver injury （DILI） induced by acetaminophen （APAP） through the endoplasmic reticulum stress pathway. MethodSixty C57BL/6N mice were randomly divided into normal group， model group， silybin group （3.4 g·kg-1）， and high-， medium- and low-dose BF groups （3.0， 1.5， 0.75 g·kg-1）， with 10 mice in each group. The DILI model was induced by intragastric administration of APAP at 800 mg·kg-1， and drugs were administered simultaneously for 10 consecutive days. The serum contents or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） were measured. Hematoxylin-eosin（HE） staining was performed to observe the pathological changes in liver tissues. The morphological changes in liver mitochondria were observed by transmission electron microscopy. The activities or content of superoxide dismutase （SOD）， malondialdehyde （MDA）， total antioxidant capacity （T-AOC）， glutathione （GSH）， glutathione disulfide （GSSG）， glutathione peroxidase （GSH-Px）， and adenosine triphosphate （ATP） in the serum and liver tissues were detected by the colorimetric method. The expression of reactive oxygen species （ROS） in liver tissues was detected by immunofluorescence. The gene expression of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and c-Jun N-terminal kinase （JNK） in liver tissues was detected by Real-time quantitative polymerase chain reaction （PCR）. ResultCompared with the normal group， the model group showed increased serum activities or content of ALT， AST， TBIL， and DBIL （P<0.01）， increased MDA and GSSG contents （P<0.01）， decreased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.01）， swollen hepatocytes with inflammatory infiltration and lamellar necrosis， swollen and broken mitochondria of hepatocytes， and increased mRNA expression of GRP78， CHOP， and JNK （P<0.01）. Compared with the model group， the groups with drug intervention showed decreased serum content or activities of ALT， AST， TBIL， and DBIL （P<0.05， P<0.01）， reduced MDA and GSSG contents（P<0.05， P<0.01）， and increased contents or activities of SOD， T-AOC， GSH， GSH-Px， and ATP （P<0.05， P<0.01）， improved swollen hepatocytes， inflammatory infiltration， and lamellar necrosis， recovered bilayer membrane structure in mitochondria of hepatocytes， and decreased mRNA expression of GRP78， CHOP， and JNK （P<0.05， P<0.01）. ConclusionBF has preventive and therapeutic effects on APAP-induced DILI mice， and the mechanism may be related to the reduction of endoplasmic reticulum stress and oxidative stress level in vivo.
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OBJECTIVE: To observe the effects of Modified Rhizoma Alismatis decoction on the expression of aquaporin 8 (AQP8) in liver tissue of hyperlipemia model rats, and to investigate the mechanism of preventing and treating hyperlipemia.METHODS: Total of 60 rats were randomly divided into blank control group (distilled water), model group, positive control group (simvastatin 1. 89 mg/kg) and modified Rhizoma Alismatis decoction high-dose, medium-dose and low-dose groups (29. 56, 14. 78, 7. 39 g/kg, calculated by crude drug), with 10 rats in each group. Those groups were given high-fat diet to induce hyperlipemia model and given relevant medicine intragastrically once a day for consecutive 5 weeks except that blank control group was given normal diet. After administration, the serum contents of TG, TC, HDL-C and LDL-C in rats were detected, and the pathomorphology changes of liver tissue were observed; the mRNA and protein expression of AQP8 in liver tissue were detected. RESULTS: Compared blank control group, the serum contents of TG, TC and LDL-C in model group were increased significantly (P<0. 05 or P<0. 01),while the serum content of HDL-C was decreased significantly (P<0. 01); pathological changes were found in liver tissue, such as irregular cell arrangement and hepatic sinusoidal hyperemia and edema; mRNA and protein expression of AQP8 in liver tissue were increased significantly (P<0. 01). Compared with model group, above indexes of treatment groups were improved significantly (P<0. 05 or P<0. 01); the structure of liver tissue tended to be normal and the fatty degeneration was obviously alleviated. CONCLUSIONS: Modified Rhizoma Alismatis decoction can regulate the mRNA and protein expression of AQP8 in liver tissue so as to play the effects on the prevention and treatment of hyperlipidemia.
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Objective To explore the effect of vitamin K2 on β-glycerophosphate(β-GP)-induced rat vascular smooth muscle cells (VSMCs) calcification and and the mechanism.Methods VSMCs were obtained from rat aortic,and identified by immunocytochemistry,then randomly divided into control group,high phosphorus group,vitamin K2 group (the group was settled three subgroups according to the concentration of vitamin K2 based on the high phosphorus medium,namely 10 μmol/L,25 μmol/L,50 μmol/L) and noggin (bone morphogenetic protein pathway inhibitor) group.Calcification was visualized by Alizarin red staining,calcium load in cells was quantified by o-cresolphthalein complexone method and alkaline phosphatase (ALP) activity was measured after stimulating 14 days,gene expressions of bone morphogenetic protein-2 (BMP-2),SMAD1,SMAD7 and Runx2 mRNA were detected by RT-PCR,Runx2 protein levels was detected by Western blotting after stimulating 3 days.Results Compared with the cells in control group,high phosphorus induced cell calcification,increased ALP activity,up-regulated the expression of BMP-2,SMAD1,Runx2 mRNA (P ＜ 0.05) and down-regulated the expression of SMAD7 (P ＜ 0.01),while compared with high phosphorus group,the calcium deposition,ALP activity and the expression of BMP-2,SMAD1,Runx2 mRNA were remarkably reduced in a dose-dependent manner by treatment with vitamin K2 (P ＜ 0.05) and the expression of SMAD7 was increased (P ＜ 0.01).Compared with high phosphorus group,SMAD1 and Runx2 expression in noggin group were remarkably reduced(P ＜ 0.01).Conclusion Vitamin K2 inhibits β-glycerophosphate-induced VSMCs calcification which correlates with the suppression of the expression of osteoblast markers through the down-regulation of bone morphogenetic protein pathway.