RESUMO
Objective: To observe the effect of Prunellae Spica extracts (PS) on the lipid metabolism in Zuker Diabetes Fatty (ZDF) rats based on AMP-activated protein kinase/acetyl CoA carboxylase (AMPK/ACC) signaling pathway.Method: The 32 male ZDF (fa/fa) type 2 diabetic rats were randomly divided into model group,metformin group (180 mg·kg-1·d-1),and low and high-dose PS groups (12.25,24.5 mg·kg-1·d-1),with 8 in each group.8 male Zuker Lean (ZL) rats were selected as normal group.Body weight and fasting blood glucose were monitored at the 0th,4th and 8th weeks after administration.After 8 weeks,abdominal aorta blood was collected,serum was frozen at-20℃ by centrifugation,liver tissue was frozen at-80℃,fixed with 4% paraformaldehyde and embedded in paraffin.Serum triglyceride (TG),cholesterol (CHO),low density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA) levels were measured by radioimmunoassay.Fat droplets in hepatocytes were measured by oil red O staining.Gene expressions of AMP-activated protein kinase-alpha 2(AMPKα2),Acetyl CoA carboxylase (ACC) in liver were detected by real-time polymerase chain reaction (Real-time PCR).Protein expressions of p-AMPKα were observed by immuno-histochemical (IHC) method.Result: Compared with the normal group,the T2DM model group showed significant increases in serum levels of TG,CHO,LDL-C,FFA and lipid droplets in hepatocytes.AMPKα2 mRNA expression was decreased,while ACC1 and ACC2 mRNA expressions were increased significantly.p-AMPKα protein expression in liver was decreased significantly (PPα2,down-regulation in mRNA expressions of ACC1 and ACC2,and up-regulation in protein expression of p-AMPKα(PPConclusion:PS can effectively improve liver lipid metabolism in ZDF rats.Its mechanism may be related to the regulation of AMPK/ACC signaling pathway in liver.
RESUMO
Objective:To observe the effect of Chaibei Zhixian decoction and peimine on Carbamazepine (CBZ) concentration, P-glycoprotein (P-gp) and multi drug resistance 1(MDR1) expression in the brain tissues of rats with refractory epilepsy, and to understand the contribution of Peimine in the compound prescription to treat the refractory epilepsy. Method:Epilepsy rat models were established by injecting kainic acid (KA) in the lateral ventricle. The successfully modeled rats were randomly divided into model group, CBZ group(0.12 g·kg-1),Chaibei Zhixian decoction+CBZ group(8.39 g·kg-1+0.12 g·kg-1), peimine+CBZ group(0.01 g·kg-1+0.12 g·kg-1) and sham operation group. After 60 days of intervention, the expression levels of P-glycoprotein (P-gp) and MDR1b mRNA in the brain cortex were detected by Western blot and quantitative real\|time fluorescence polymerase chain reaction(Real-time PCR),the contents of CBZ and 10,11-epoxidation of carbamazepine (CBZE) were measured by liquid chromatography-mass spectrometry (LC-MS). Result:Compared with sham group, the expression of P-gp/MDR1 in the cortex of model group was significantly increased (PPPPPPPConclusion:Chaibei Zhixian decoction and peimine may increase the content of CBZ and CBZE in the brain tissues in rats with intractable epilepsy by reducing the expression of MDR1/P-gp in the cortex.