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@# Objective： ：To study the regulatory effect of mogrol (MO) on lipid metabolism of hepatic cancer cells and its molecular mechanism. Methods: Oleic acid (OA) was used to induce fat accumulation in hepatocellular carcinoma HepG2 cells and to establish a steatosis cell model. CCK-8 method was used to detect the cytotoxicity of MO to HepG2 cells, and an experimental working concentration without obvious cytotoxicity of MO was chosen. After being treated with different concentrations of MO, lipid accumulation in the cells was observed by oil red O staining, and the contents of triglyceride (TG) and cholesterol (TC) in the cells were measured. Key genes involving in lipid metabolism were screened out by high-throughput transcriptome sequencing qPCR was used to detect the mRNA expressions of ,SREBP-1c and FASN, while Western Blot was used to detect the protein expressions of p-AMPKα, SREBP-1c and FASN in cells of model group and treatment group. Results: After OA induction, a large amount of lipids accumulated in HepG2 cells, the contents of TG and TC increased significantly. Three key genes (SREBP-1c, FASN and p-AMPK α) involving in lipid metabolism of hepatic cancer cells were screened out. After OA induction, the mRNA expressions of SREBP-1c and FASN increased, the protein expression of p-AMPK α decreased while the protein expressions of SREBP-1c, FASN and other proteins increased significantly. After intervention with working concentration of MO, intracellular lipid accumulation, contents of TG and TC, mRNA expressions of SREBP-1c, FASN and protein expressions of SREBP-1c, FASN decreased significantly, while the expression of p-AMPKα increased. Conclusion: Mogrol can inhibit the synthesis of fatty acids by activating the expression level of AMPK signaling pathway related factors SREBP-1c and FASN, so as to play the role of regulating lipid metabolism.
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Background & objectives: Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Methods: Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest X-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. Results: It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. Interpretation & conclusions: The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.
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Objective To observe the intervention effects of methylprednisolone (MPred) to acute lung injury(ALI) model of rats induced by oleic acid.Methods Thirty of Sprague-Dawley rats were randomly divided into three groups which were normal control group (NC,n =6),oleic acid model group (n =12),and MPred group (n =12).Rats were injected with oleic acid at dose of 0.1mg/ kg via caudal vein and then ALI model was established.The rats of NC group were injected with 0.1 mg/kg of normal saline instead of oleic acid.In NC group rats were sacrificed by blood collection at 6h after NS injection.Blood samples and tissues were collected and stored freezing.Samples of the other groups were collected at 2h and 6h after the last treatment.The observation indexes are histomorphology of lung tissue,the wet and dry weight of lung (W/D),index of quantitative assessment (IQA) score,partial pressure of oxygen in artery (PaO2),and SOD,MDA,MMP-9 and TIMP-1 levels in the blood plasma and lung tissue.Results Lung surface hyperemia relieved obviously and pink secretion from trachea of rats in MPred group decreased compared with oleic acid model group.In light microscope,compared with oleic acid model group,effusion of inflammatory cell in alveolar space of rats in MPred group eased.W/D of rats in oleic acid model group advanced obviously compared with that in NC group,W/D of rats in medrol group lowered obviously compared with that in oleic acid model group.IQA scores of rats in oleic acid model group advanced obviously compared with that in NC group,IQA score of rats in MPred group lowered obviously compared with that in oleic acid model group.PaO2 of rats in oleic acid model group lowered obviously compared with that in NC group,PaO2 of rats in MPred group advanced obviously compared with that in oleic acid model group.The level of SOD in plasma and lung tissue of rats in oleic acid model group lowered obviously compared with that in NC group,SOD level in plasma and lung tissue of rats in MPred group advanced obviously compared with that in oleic acid model group.The level of MDA in plasma and lung tissue of rats in oleic acid model group lowered obviously compared with that in NC group,MDA in plasma and lung tissue of rats in MPred group advanced obviously compared with that in oleic acid model group.Compared with the NC group,the level of MMP-9 in the plasma and lung tissue of oleic acid induced ALI rats increased and TIMP-1 levels decreased significantly.The level of MMP-9 in the plasma of rats decreased and TIMP-1 level increased significantly in MPred group at 2h and 6h.Conclusion MPred can improve lung pathological injury,increase PaO2 level,decrease lung W/D ratio and IQA scores by modulating the level or activity of the SOD and MDA and MMP-9 and TIMP-1 in the plasma and lung tissues.It is speculated that the effects of anti-inflammation and anti-exudation of sodium aescinate may due to affecting on oxidative stress response as well as the decomposition and remodeling of extracellular matrix during inflammatory lung injury of acute lung injury rats.