Effects Of Progesterone On Scopolamine-induced Impairment Of Spatial Working Memory In Rats

Objective : Postoperative cognitive dysfunction(POCD) refers to the common neurological complications in anesthesia in patients after operation, if handled properly, will seriously affect the prognosis of patients, especially in elderly patients with the most significant and difficult to recover. Pathological and physiological mechanisms of POCD is not exact, domestic and foreign scholars mainly put forward the hypothesis about central cholinergic system, neurotransmitters such as amino acids, surgical stress inflammation, neuronal apoptosis,α beta neurotoxicity and damage of hippocampal synaptic plasticity.The pathophysiology of POCD is not created by single factor, but rather consists of many complex factorscomprehensive action. Research shows that, the happening of POCD is related with the central cholinergic system abnormalities, application of anticholinergic drugs can significantly affect space, cognitive functions such as learning and memory.Scopolamine is an anticholinergic drug, and play a strong role in peripheral.Scopolamine will be injected into the ventral of bilateral hippocampus and the dorsal of medial thalamic of rats, in this way can reduce the rat hippocampal cholinergicneurotransmitters, while damaging space,cognitive functions such as learning and memory.Glutamic acid(Glu) is the excitatory neurotransmitter in the central nervous system in typicaliy, gamma aminobutyric acid(GABA)are inhibitory neurotransmitter typicaliy, both of them can be involved in learning, memory and other central nervous activity. Another neurosteroid progesterone(PROG) can reduce the nervous system excitable toxicity by adjusting the central amino acid neurotransmitter system, and thus play a neuroprotective role. And PROG can dependent the concentration to inhibite the neurotoxic effect induced by α beta so that improving the survival rate of neurons, and improve- ting the cognitive function.Therefore, this study intends to simulatie the suppression environment of central cholinergic system after general anesthesia by intraperitoneal injection of scopolamine of rats, to establish the rat model of POCD in parallel by progesterone intervention, and evaluate the effection of POCD in rats.Methods:40 healthy two-month-old male SD rats,weighing130~150g. Using a random number table,divide these 40 rats into four groups(n=10) : saline control group( group C),scopolamine group( group S),progesterone in the intervention group( group S + P)and pure progesterone group( group P). Group S simulate the inhibition of neurotransmitter acetylcholine environment by acetylcholine after general anesthesia by peritoneal injection of scopolamine( 1.8 mg / kg), establish the animal model of rat COPD. Group S was intraperitoneally injected scopolamine( 1.8 mg / kg). Group S + P were intraperitoneally injected with scopolamine(1. 8 mg / kg) and progesterone( 8 mg / kg). Group C was intraperitoneally injected equal volume of saline.Put the 4 groups of rats into the self-made open field test after injected the drug immediately, observe of the changes in mood and behavior of rats within 10 min before(T0)and every 10 min within 1h after intraperitoneal injection of drugs(T1-T6), record the central and peripheral run lattice number, residence time, erect inquiry behavior times, modification times, and the time of modification. In the seventh days at the end of the open field test, run the Ytype maze test to observe the changes of cognitive function such as learning and memory ability of rats. After the Y- type electric maze test the rats were killed immediately,and the hippocampal neurons were taken, hematoxylin eosin staining(HE staining) method was used to observe the morphological changes of hippocampal neurons, and Immunohistochemical method was used to determinate the content of GLU and GABA in hippocampal neurons.Results:Compared with group C,the peripheral run lattice number and the central run lattice number were increased in group S and group S+P at the time point of T1-4 after injection, and also the central cell residence time was prolonged, the number of vertical movement were increased,the modification times and the time of modification were reduced. At the seventh days, the number of total training was increased in Y- type electric maze test in rats, and the standard time was prolonged.After the Y- type electric maze test, the content of GLU was increased in hippocampal neurons of rats, and the content of GABA was decreased.The morphological structure of hippocampus neuron cell is destroyed,the boundary is blurred,cell shrinkage,the whole cell structure arranged loosely,degeneration or even death was occer,and the pathological injury was aggravated(P<0.05).No significant differences in the P group(P>0.05).Compared with group S, the peripheral run lattice number and the central run lattice number were reduced in group S+P at the time point of T1-4 after injection,and also the central cell residence time was reduced, the number of vertical movement were reduced,the modification times and the time of modification were increased. At the seventh days, the number of total training was reduced in Y- type electric maze test in rats, and the standard time was reduced. After the Y- type electric maze test, the content of GLU was reduced in hippocampal neurons of rats,and the content of GABA was increased.The morphological structure of hippocampus neuron cell is destroyed,cell swelling, the situation of morphology incompletely and arrangement was improved, the degeneration and necrosis of neurons were decreased, and the pathological injury was reduced(P<0.05).Conclusion: Intraperitoneal injection of progesterone can ameliorate scopolamine induced delirium symptoms,probably be related to the acetylcholine in vivo of rats and the balance disorders between GLU and GABA.