1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.
2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.
3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos. 相似文献
Summary Bayesian analysis is given of a random effects binary probit model that allows for heteroscedasticity. Real and simulated examples illustrate the approach and show that ignoring heteroscedasticity when it exists may lead to biased estimates and poor prediction. The computation is carried out by an efficient Markov chain Monte Carlo sampling scheme that generates the parameters in blocks. We use the Bayes factor, cross‐validation of the predictive density, the deviance information criterion and Receiver Operating Characteristic (ROC) curves for model comparison. 相似文献
Objective To observe the effect of intrathecal clonidine plus morphine on expression of protein kinase A (PKA) catalytic subunit in the spinal dorsal horn in a rat model of incisional pain. Methods Eighty male Sprague-Dawley rats were divided randomly into five groups: sham group, control group, pre-incisional morphine 2.5 μg group, pro-incisional clonidine 5 μg group and preincisional morphine 2.5 μg plus clonidine 5 lag group (n=16). lntrathecal catheter and the model of incisional pain were pro-duced according to Yaksh and Brennan's described method respectively. Changes of pain behavior were assessed by mechanical with-drawal threshold (MWT) and thermal withdrawal latency(TWL). The expressions of PKA catalytic subunit in the spinal dorsal horn were assessed by immunohistochemical method and western blotting analysis. Results Compared with sham group, MWT and TWL in control group were decreased significantly at 2 h after incision (P<0.01) and the number of positive cells and protein expression of PKA catalytic subunit in the spinal dorsal horn were increased significantly in control group (P<0.01). Compared with control group, MWT and TWL in pre-incision morphine 2 μg plus clonidine 5 lag group were increased significantly at 2 h after incision (P<0.01) and the number of positive cells and protein expression of PKA catalytic subunit in the spinal dorsal horn were decreased significantly in pre-incision morphine 2 μg plus clonidine 5 μg group (P<0.01). However, MWT, TWL and the number of positive cells and pro-tein expression of PKA catalytic subunit in the spinal dorsal horn changed with no statistical significance in pre-incisional morphine 2.5 μg group and pre-incisional clonidine 5 μg group compared with control group. Conclusion lntrathecal clonidine significantly enhances the antinociceptive effect of intrathecal morphine in a rat model of incisional pain, which might be associated with inhibi-tion of the increased expression of PKA catalytic subunit in spinal cord. 相似文献