Perfluorooctanoic acid-induced lipid metabolism disorder in SD rat liver and its effect on the expression of fatty acid metabolism-related proteins. / å ¨æ°Ÿè¾›é ¸å¯¹SDå¤§é¼ è‚è„‚è´¨ä»£è°¢ç´Šä¹±åŠè„‚è‚ªé ¸ä»£è°¢ç›¸å ³è›‹ç™½è¡¨è¾¾çš„å½±å“.

OBJECTIVES: Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR. METHODS: A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH2O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting. RESULTS: After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05). CONCLUSIONS: PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.

[Effects of perfluorooctanoic acid on oxidative stress and PPARα and its related CYP4A1 gene expression in rat liver].

OBJECTIVE: To study the effects on oxidative stress and the expression of PPARα-related genes and protein in the liver of rats induced by pentadecafluorooctanoic acid( PFOA). METHODS: A total of 28 male SD rats were randomly divided into four groups: control group: double distilled water, low dose group: PFOA 1 mg/( kg·d), middle dose group: PFOA 5 mg/( kg·d), high dose group: PFOA 25 mg/( kg·d), and were administrated by gavage once a day for 14 days take the organization after anesthesia, according to the follow-up experiments need treatment. The activity of oxidative stressrelated enzymes and the content of malondialdehyde( MDA) in liver tissue were detected. The mRNA levels of peroxisome proliferators-activited receptors α( PPARα) and cytochrome P4504A1( CYP4A1) were detected by real-time PCR. The protein expression of PPARα was detected by Western blot. RESULTS: There was significant difference between high dose group and control group of the body weight( P < 0. 05). The liver weight and relative liver weight of the middle and high dose groups were significantly higher than those of the control group( P < 0. 05). The activity of superoxide dismutase( SOD) and glutathione peroxidase( GSH-Px) in the liver of the low dose group were significantly higher than that of the control group( P < 0. 05). The content of MDA in liver of middle and high dose groups were increased by 2. 5 times and 3. 5 times compared with that of control group( P < 0. 05). The expression of PPARα and its regulated CYP4A1 mRNA were significantly increased in low, middle and high dose groups. The expression of PPARα protein in the low, middle and high dose groups were up-regulated. CONCLUSION: PFOA exposure can lead to oxidative stress in rat liver, resulting in antioxidant enzymes SOD and GSH-Px and MDA changes. At the same time, PFOA exposure induced up regulation of PPARα and CYP4A1 in the liver of rats to enhance theß-oxidation of fatty acids, leading to lipid peroxidation, which has obvious toxic effects on rat liver.