ABSTRACT
Objective:To observe the changes of leptin receptor-tyrosine kinase Janus2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway and the regulatory effect of Xiaoyaosan on the hypothalamic arcuate nuclei of rats with chronic mild unpredictable stress model （CUMS）. Method:Sixty male sprague-dawley rats were randomly divided into normal group， model group， Xiaoyaosan group， and fluoxetine group. After one-week adaptive feeding， the rats in model group， Xiaoyaosan group and fluoxetine group were uesd to replicate the chronic psychological stress rat model through mild unpredictable stimulation. Meanwhile ， they were simultaneously administered the corresponding drugs， Xiaoyaosan 19.27 g·kg-1·d-1， Fluoxetine 2 mg·kg-1·d-1 （based on the average adult body weight of 60 kg）， the rats in the normal group and the model group were given the same volume of normal saline for 6 weeks. The body weight， food intake， sucrose consumption ratios， and the experimental behavior in the open field test （OFT） of the groups were observed. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expressions of ob-R， JAK2， and STAT3 in the arcuate nucleus of rat hypothalamus. Result:Compared with the normal group， the body weight and food intake of the model group were significantly decreased （P<0.05， P<0.01）， the sucrose consumption ratios ， the total behavioral distance of the experimental field and the total distance of the central area were significantly reduced， the protein and mRNA expressions of ob-R， JAK2， STAT3 in the arcuate nucleus of hypothalamus in rats increased significantly （P<0.05， P<0.01）. Compared with the model group， the body weight of Xiaoyaosan group increased significantly on the 7th， 14th， 21st and 28th days （P<0.05， P<0.01）， the food intake of rats increased significantly on the 21st and 35th days of the experiment （P<0.05）， and the sucrose consumption ratios， the total distance of the experimental behavior in the open field test （OFT） and the total distance of the central area were significantly improved. Xiaoyaosan had a corresponding regulatory effect on the protein and mRNA expressions of ob-R， JAK2， STAT3 in the arcuate nucleus of hypothalamus in model rats （P<0.05， P<0.01）. Conclusion:Xiaoyaosan regulates the body weight， appetite， and energy metabolism of chronically mild and unpredictable stress rats， which may be related to the ob-R-JAK2/STAT3 pathway in the hypothalamic arcuate nucleus.
ABSTRACT
Objective:To observe the preventive and therapeutic effects of 5-week administration with Xiaoyaosan on rat liver injury caused by tripterygium Glycosides. Method:Thirty-one SD rats were randomly divided into 4 groups， namely normal group， tripterygium glycosides group， tripterygium glycosides+Xiaoyaosan group （treatment group）， and tripterygium glycosides+Xiaoyaosan for 1 week in advance group （prevention group）. Tripterygium glycosides （37.5 mg·kg-1） was administered intragastrically， and Xiaoyaosan （water decoction， 19.270 g·kg-1） was administered intrastrically. First， the rats of prevention group were intragastrically administrated with Xiaoyaosan at 8：00-9：00 am， and the rats of other groups were given an equal volume of normal saline. After 1 week， the rats of tripterygium glycosides group were administered intragastrically with tripterygium glycosides suspension at 8：00-9：00 am. The rats of the treatment group and the prevention group were intragastrically administrated with Xiaoyaosan at 8：00-9：00 am， and then tripterygium glycosides suspension 2 hours later. All the drugs were given once a day for 5 weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of liver， enzyme-linked immunosorbent assay （ELISA） was used to detect serum interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， chemical method was used to detect the content changes of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， glutathione peroxidase （GSH-Px）， superoxide dismu-tase （SOD）， trace malondiamine aldehyde （MDA）. Immunohist-ochemical staining was used to observe the expressions of IL-6， IL-1β and TNF-α in liver tissue. Result:Compared with the normal group， the tripterygium glycosides group showed inflammatory cell infiltration， hepatocyte edema， hepatic sinuses squeezing and narrowing， liver plate widening， and liver cell necrosis， the contents of serum IL-1β， IL-6， TNF-α， ALT， AST and MDA were significantly increased（P<0.01）， but the contents of GSH-Px and SOD were decreased significantly （P<0.05， P<0.01）， while the positive expressions of IL-6， TNF-α， IL-1β in liver tissue were significantly increased （P<0.01）. Compared with tripterygium glycosides group， rats in the treatment group and the prevention group had less inflammatory cells infiltration and reduced edema in the liver tissue， and disorders in some cell， the contents of serum IL-1β， IL-6， TNF-α， ALT， AST， MDA were significantly decreased （P<0.01）， the contents of GSH-Px and SOD were significantly increased （P<0.05）， and the positive expressions of IL-6， TNF-α， IL-1β in liver tissues were significantly decreased （P<0.01）， with a better efficacy in the prevention group. Conclusion:Xiaoyaosan can obviously alleviate the long-term liver toxicity caused by tripterygium polyglycoside to a certain extent， with a better prophylactic effect.