Study On The Improvement Of Tetrahydroxy Stilbene Glucoside On Global Cerebral Ischemia Reperfusion Injury In Gerbils Hippocampus

Ischemic cerebral diseases and consequential vascular dementia has become one of thehealth-risky incidents. Thrombolytic therapy has been widely used to treat ischemiccerebral diseases, however, ischemia-reperfusion (I/R) injury following thrombolysis isan intricate problem in clinic. Reperfusion after ischemia aggravates cerebral injury,although it is essential for recovery of neuronal function. A large amount of reactiveoxygen species (ROS) will emerge after I/R, which injures neuronal mitochondria byinitiating mitochondria-dependent apoptosis pathway and ultimately causes neuronapoptosis and loss.Tetrahydroxy stilbene glucoside (TSG) is one of the water-soluble active ingredients ofpolygonum multiflorum. Previous studies had demonstrated that TSG had manyphysiological functions, including ameliorated atherosclerosis, protected liver injury,prevented dementia, scavenged ROS, dilated vessels, decreased cholesterol, suppressedtumor and so on. In addition, TSG could inhibit ROS production and recover learningand memory capacity after I/R in gerbils. Because of the hippocampal CA1regionoccupies an important place in learning and memory function, but the effect of TSG onI/R-induced neuronal apoptosis, especially in hippocampal CA1region, and underlyingmechanisms are not fully understood.Objective: To investigate the protective effects of TSG on I/R-induced hippocampalinjury and underlying mechanisms in gerbils and further provide theoretical andexperimental basis for TSG usage in cerebral I/R injury therapy in clinic. Methods: Gerbil global I/R model was established by bilateral ligation of carotidarteries for30min followed by reperfusion for5days.36animals were divided into6groups randomly: Sham, I/R model, I/R+TSG high (6mg/kg weight), I/R+TSG middle(3mg/kg weight), I/R+TSG low (1.5mg/kg weight) and edaravone injection group (3mg/kg). The functions of learning and memory were detected by Morris water maze in5days after reperfusion. The activity of SOD and GSH-Px enzymes and the content ofMDA in cerebral tissue were assessed by ELISA. The number and structure of neuronsand neuronal apoptosis in hippocampal CA1region was evaluated by Nissl and TUNELstaining, respectively. In addition, the expression of active-caspase-3in cerebral tissueswas measured by Western blot analysis.Results: Compared to Sham group, learning and memory capacity of gerbils in I/Rmodel group declined significantly, the number of functional neurons in hippocampalCA1region decreased significantly. The activity of SOD and GSH-Px in cerebraltissues decreased observably, while, MDA content increased significantly. Furthermore,the apoptotic neurons indicated by TUNEL staining as well as caspase-3activationincreased observably. TSG administration at middle and high dose (3,6mg/kg) andedaravone injection significantly reversed aforementioned changes induced by I/R. Incontrast, TSG administration at low dose (1.5mg/kg) had no obvious improvement.Conclusion: TSG has therapeutic effects on I/R induced cerebral injury, especially ondelayed neuron apoptosis in hippocampal CA1region, which may be related to itssuppression effect on caspase-3activation.