1.Endoplasmic reticulum stress-mediated high-fat diet, palmitic acid-induced insulin resistance in skeletal muscle and interventional effects of fenofibrate
Yingying BAO ; Yunxia LU ; Guanjun CHEN ; Jingjing CHENG ; Qiu ZHANG
Chinese Pharmacological Bulletin 2014;(11):1557-1563
Aim To investigate endoplasmic reticulum stress ( ERS)-mediated high-fat diet and palmitic acid-induced insulin resistance ( IR) in skeletal muscle and interventional effects of fenofibrate both in vivo and in vitro tests. Methods Female SD rats were randomly subjected to a standard control diet ( SCD) or high-fat diet ( HFD) for 20 weeks, then the HFD group was di-vided into high-fat-diet group and high-fat-diet group treated with fenofibrate ( HFD +FF, 30 mg · kg-1 · d-1 ) for another 8 weeks. The changes of IR and ex-pression of peroxisome proliferator-activated receptor α( PPARα) , glucose regulated protein 78 ( GRP78 ) and transcription factors GADD153 ( CHOP ) were as-sessed respectively. C2C12 myotubes were divided into normal control group ( NC ) , model group ( palmitic acid, PA) , postive control drug group ( tunicamycin, TM) and treatment group ( fenofibric acid, FA+PA) , the expressions of GRP78 and CHOP were assessed re-spectively. Insulin-stimulated phosphorylation of Akt was also analyzed to detect changes of insulin sensitivi-ty in C2 C12 . Results The high-fat diet induced obvi-ous IR and upregulated ERS markers GRP78 and CHOP in skeletal muscle of rats, and these responses were attenuated by treatment with fenofibrate. Incuba-tion of myotubes with palmitic acid or tunicamycin sig-nificantly increased expression of ERS markers GRP78 and CHOP. Meanwhile, insulin-stimulated phosphoryl-ation of Akt was inhibited obviously. Pre-incubation with FA markedly inverted PA-induced ERS and insu-lin-stimulated phosphorylation of Akt. Conclusion Fenofibrate ( fenofibric acid) has obvious effects of IR on skeletal muscle tissues and cells, which may be re-lated with reduced expression of GRP78 and CHOP in ERS.
2.Experimental study on the curative effect of Huoxue-Tongluo-Zhitong ointment treating acute soft issue injury
Liming WANG ; Qingyuan TAN ; Yan ZHANG ; Guanjun QIU ; Hongxue QU ; Weidong ZHANG
International Journal of Traditional Chinese Medicine 2011;33(10):893-896
Objective To observe the curative effect of Huoxue-Tongluo-Zhitong ointment treating soft tissue injury,and the safety of application on skin.Methods The treatment group was treated with Huoxue-Tongluo-Zhitong ointment,while the comparison group was treated with Votalin Pill.Acute toxicity experiment,irritant experiment and hypersensitivity experiment of skin were performed on New Zealand white rabbits.Results Huoxue-Tongluo-Zhitong ointment decreased local edema and leukocyte effusion,accelerate the re-absorption of hematomas.On injury signs index,group A [ (0.32± 0.35),(0.29± 0.27) ] was better than group B [ (0.58±0.42),(0.91 ±0.34) ] (P<0.05).The pathological process in group A and B was obviously reduced than group C (P<0.05).In the neutruphil infiltration density measuring:compared with group C,group A and B both showed significant difference (P<0.05),but there was no significant difference between group A and B (P>0.05).Conclusion Huoxue-Tongluo-Zhitong ointment performed well on the treatment of soft issue injury,with no toxicity,irritation,and hypersensitivity of skin,as well as high safety of administration.