Study On The Effective Compatibility Dose And The Energy Metabolism And The JAK/STAT Signaling Mechanism Of Effective Ingredients In Astragalus And Notoginseng On Cerebral Ischemia-Reperfusion

Objective:To explore the effective compatibility dosis of astragaloside, ginsenoside Rg1, ginsenoside Rb1,and notoginsenoside Rl affecting oxidative stress and energy metabolism after ischemia-reperfusion in mice through orthogonal experiment, and thus provide the basis for the laboratory and clinical research. Then,based on the effective compatibility dose energy,the study on the energy metabolism and the mechanism of JAK/STAT signaling in the cerebral ischemia mice reperfused was carried out.Method:(1)Male C57BL/6mice were randomly divided into the nine experimental group and a sham group through L9(34) orthogonal experiment, and administration3d continually. Ligation of bilateral carotid arteries causing cerebral ischemia20min, and reperfusion30min established cerebral ischemia reperfusion model. The content of malondialdehyde (MDA) and glutathione (GSH), as well as activity of superoxide disnnutase (SOD) in brain tissue were measured, and content of adenosine triphosphate (ATP) in brain tissue was determined by high performance liquid chromatography (HPLC).(2)88male C57BL/6mice being randomly divided into10experimental group and a sham group, were administered continuously for three days,whose bilateral carotid artery were ligatured to cause cerebral ischemia for20min, and then Reperfusion drug for24h. When the cerebral ischemia reperfusion model was established, brains were removed,Then determining the indicators of energy metabolism:The adenosine triphosphate(ATP), adenosine diphosphate(ADP), adenosine monophosphone(AMP),total adenine nucleotides(TAN) levels and the energy charge(EC),then studing the JAK/STAT signaling mechanism (the determination of JAK1, STAT1, GLUT3by western blot)Result:Assignment of different weights to each index (ATP:0.3, SOD:0.25, MDA:0.25, GSH:0.2), comprehensive weight scoring of various indexes were calculated, all of the astragaloside, ginsenosides Rg1, ginsenoside Rbl and notoginsenoside R1in Astragalus and Notoginseng protected cerebral ischemia-reperfusion injury, four effective ingredients had the best compatibility dose; Reperfusion the drug four combining active ingredients cerebral ischemia rats after24h, the levels of ATP, ADP, AMP, TAN and EC and GLUT3in brain tissue improved significantly (P <0.05), and the content of p-JAK1, p-STAT1reduced (P<0.05). Conclusion:The best compatibility dose of four effective ingredients in Astragalus and Notoginseng were astragaloside:40mg/kg, ginsenosides Rgl:50mg/kg, ginsenosides Rbl:40mg/kg, notoginsenoside Rl:1Omg/kg; Combination of four active ingredients can is effective to inhibit the activation of the JAK/STAT signaling pathway and to promote brain glucose utilization, which play a protective role in cerebral ischemia...