ABSTRACT
Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L−1). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L−1), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L−1 after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L−1, respectively (P<0.05). After exposure to 30 mmol·L−1 and 100 mmol·L−1 DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L−1 DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L−1 group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L−1 DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L−1 and 100 mmol·L−1 can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.
ABSTRACT
Objective To research into the prevention and care of the early stage serious complication caused by hypertensive cerebral hemorrhage,aiming at reducing the death rate and disability rate caused by the illness,and raising the survivors living quality.MethodsBy analysing the serious complication of 90 hyertensive cerebral hemorrhage patients confirmed by CT and the information of prevention and care.Results85 patients had high pressure in the cranial cavity;8 patients had brain hernia;18 patients had heart failure;2 patients had myocardial infarction;8 patients had brain and heart syndrome;3 patients had lung oedema;14 patients had lungs infected;22 patients,kidneys didn,t funtion fully.20 patients bleed in the alimentary canal;38 patients had high blood sugar.51 patients survived,and 39 patients died.The death rate caused by the illness was 43.3%.ConclusionThe incidence of the hypertensive cerebral hemorrhage is high.Has much complication the death rate and disability rate caused by the illness are high.So we should pay attention to the prevention and care of early stage serious the complication of hypertensive cerebral hemorrhage,Control the blood pressure effectively to reduce the serious complication,Death rate and disability rate and improve the prognoses.