Changes of liver lipid metabolism-related PPAR-γ/LXR-α/ABCG1 pathways and inflammatory factors in atherosclerotic mice and role of Huayu-Qutan recipe

AIM To observe the changes of liver lipid metabolism-related peroxisome proliferator-activated receptor-γ (PPAR-γ)/liver X receptor-α (LXR-α)/ATP-binding cassette transporter G1 (ABCG1) signaling pathways and inflammatory factors in mice with atherosclerosis (AS), and to investigate the effects of Huayu-Qutan recipe (HYQT) on hepatic lipid metabolism and inflammatory response and the mechanisms. METHODS ApoE^-/- mice (n=24) were randomly divided into model group, HYQT group and simvastatin group, and C57BL/6J mice (n=8) were used as control group. Except for the control group, the mice in other groups were given high-fat diet. After 12 weeks of modeling, the mice in HYQT and simvastatin groups were intragastrically given the corresponding drugs, and the mice in control and model groups were given the same volume of normal saline. After 8 weeks, the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by an automatic biochemical analyzer. HE and oil red O staining was used to observe liver histopathological and lipid changes. The hepatic levels of free fatty acid (FFA), TG, tumor necrosis factor-α (TNF-α), Toll-like receptor 4 (TLR4) and interleukin-1β (IL-1β) were detected by ELISA. The protein expression of PPAR-γ, LXR-α and ABCG1 was determined by Western blot. RESULTS Compared with control group, the serum levels of TC, TG and LDL-C in model group were significantly increased (P<0.01), and the HDL-C content was significantly decreased (P<0.01). Liver steatosis, cell size augmentation and lipid deposition were obvious, and liver FFA and TG levels were significantly increased (P<0.01). The liver levels of TLR4, TNF-α and IL-1β were significantly increased (P<0.01), while the protein expression of PPAR-γ, LXR-α and ABCG1 was significantly decreased (P<0.05 or P<0.01). Compared with model group, the serum levels of TC, TG and LDL-C in simvastatin group and HYQT group were significantly decreased (P<0.05 or P<0.01), and the HDL-C content was significantly increased (P<0.01). Liver steatosis was weakened, and liver lipid deposition and FFA and TG levels were significantly decreased (P<0.05 or P<0.01). The liver levels of TLR4, TNF-α and IL-1β were significantly decreased (P<0.01), while the protein expression of PPAR-γ, LXR-α and ABCG1 was significantly increased (P<0.05 or P<0.01). CONCLUSION Huayu-Qutan recipe may exert anti-AS effect by regulating liver PPAR-γ/LXR-α/ABCG1 pathways and attenuating liver TRL4-mediated inflammatory responses.     

Activation of α7nAChR promotes wound healing in diabetic mice by suppressing TNF-α expression

AIM: To explore the role of α7 nicotinic acetylcholine receptor (α7nAChR)-specific agonist PNU-282987 in promoting wound healing in diabetic mice by suppressing the expression of tumor necrosis factor α （TNF-α）.METHODS: A model of incised wound was established in diabetic mice or normoglycaemic mice (control). Skin samples were taken on 1 d, 3 d, 5 d, 10 d, 14 d and 21 d post-injury (5 mice in each posttraumatic interval). The numbers of macrophages and fibroblasts, the expression of TNF-α and the deposition of collagen were detected by the methods of immunohistochemistry, Western blotting and Masson staining, respectively. After incised wound was performed in the diabetic mice, PNU-282987 was applied by intraperitoneal injection at suitable posttraumatic interval. The above indexes were investigated again.RESULTS: Compared with control group, the diabetic mice presented delayed wound healing. In diabe-tic mice, the infiltration of macrophages and the expression of TNF-α were significantly reduced in the early phase during wound healing, while they were significantly increased from 5 d post-injury. Besides, from 5 d to 21 d post-injury, the wounds in diabetic mice showed decreased number of fibroblasts and deposition of collagen. From 5 d post-injury, PNU-282987 was applied to diabetic mice, which significantly down-regulated the expression of TNF-α, and increased the number of fibroblasts and the content of collagen in the wounds, eventually promoted wound healing.CONCLUSION: Inflammatory reactions delay wound healing in diabetic mice. Activation of α7nAChR promotes wound healing in diabetic mice by suppressing the expression of TNF-α.