The Study On The Correlation Between Activity Of Serum Adenosine And Seizures Of Epilepsy

Epilepsy is a common and easy to recurrent disease of nervous system, high disability rate, long disease, the world’s epilepsy patients with tens of millions of people, China as a big country, epilepsy patients have about 9000000, epileptic seizures not only to the patients themselves and family caused great pain and psychological burden, but also to the family, the community has brought a heavy economic burden. Epilepsy is a chronic disease of the brain, which is characterized by the transient central nervous system caused by excessive discharge. Recently, many scholars have made research on the etiology, pathogenesis and pathological changes and treatment of epilepsy. At present, there is a general correlation between the occurrence of epilepsy and synaptic remodeling, neurotransmitter receptors, glial cells, ion channels, genetic factors, and so on. At the beginning of the epileptic discharge, the membrane was accompanied by the abnormal transmembrane movement of the ion. The discharge of the discharge was gradually spread through the synaptic connection and easy to change. However, the specific mechanism of epileptic seizures is not clear, and the specific mechanism of the onset and termination of the seizure is not clarified. There is no significant effect on the application of a variety of anti epilepsy drugs for many patients with intractable epilepsy, which still need to find a new pharmacological target. Therefore, it is important to study the mechanism of epilepsy and to study the new pharmacological targets, and to improve the prognosis of patients with epilepsy and to reduce the mortality.Many related studies indicate that adenosine system is an important anti epilepsy and brain protection system in brain tissue. Adenosine and G protein coupled adenosine receptors interact to inhibit neuronal activity in the brain tissue, and acute seizures after acute seizures, the seizure termination, the adenosine system is known as the "endogenous anti epilepsy system", soluble nucleotides can interact with the extracellular nucleoside acid enzymes to produce adenosine and play an important role in the seizure of epilepsy. At present, the relationship between the activity of adenosine and the epilepsy has caused the attention of medical workers.At present, after seizures, patients serum ATP, ADP and AMP hydrolysis rate changes and serum soluble nucleotide phosphodiesterase activities change rarely reported. Different seizure types of serum ATP, ADP and AMP hydrolysis rate changes and serum soluble nucleotide phosphodiesterase activities change if the same has not been reported. This paper mainly uses the prospective study included 65 patients with epilepsy(GTCS 33 cases, partial seizures32 cases) and 35 cases of normal healthy controls, from the first chapter and the second chapter two chapter separately discusses the different types of seizure onset at different time points before and after ATP, ADP and serum AMP hydrolysis in different seizure the type of attack at different time points before and after the changes of serum soluble phosphodiesterase activity, to explore the relationship between ATPase activities and epileptic seizures and seizure type ATPase activities have no differences, to further explore the role in the activity of adenosine acid mechanism in the process of epilepsy, and in-depth understanding of the sensitivity to adenosine enzyme activity in different types of seizures, to provide the basis for clinical drug selection;The third chapter through the amygdala kindling epileptic rat model was built, and to analyze on kindling epilepsy rats in different time intervals of hippocampal neurons histopathological and apoptosis effect and to explore the relationship between adenosine A1 R and hippocampus neurons injury and to understand its protective effect on the brain, which can be more profound understanding adenosine A1 R and epilepsy, and to provide reference for the treatment of epilepsy.Chapter1 The changes of ATP, ADP and AMP in the serum of patients with epilepsy of different seizure types in interictal and post-epileptic acttack Aim:To investigate the changes of ATP, ADP and AMP in the serum of patients with epilepsy of different seizure types, and to analyze the relationship between ATP, ADP and AMP. Methods:From Mar 2014 to Dec 2015, 65 patients with epilepsy in our hospital were enrolled in the treatment of epilepsy patients. In the same period in our hospital outpatient service routine physical examination of 35 cases of normal control group. By Ultraviolet rays absorption spetrophotometry, the changes of AMP, ADP and ATP hydrolysis rate of 5 minute, 10 minute, 30 minute, 60 minute, 20 minute and 10 h in case group were observed. The changes of AMP, ADP and ATP hydrolysis rate of 5 minute, 10 minute, 20 minute and 10 h in comprehensive seizures were observed, compared with partial seizures. All data analysis used SPSS21.0 software package, P < 0.05, for the difference was statistically significant. Results:1.Patients, there was no significant difference in the AMP(ATP), ADP, and the control group(P > 0.05);2.5min, the ADP、 ATP and AMP were significantly increased, and the hydrolysis rate of ATP reached the peak at 20 min after the attack, then decreased gradually, and reached a peak at 5 ADP after the onset of H, and decreased with the increase of 60 min to the level of AMP(P<0.05);3. Compared with the partial seizure group, the 5min, the 20 min of the serum ATP, the rate of hydrolysis of ADP, and the rate of hydrolysis of AMP were significantly higher than that in the group of complete seizures and partial seizures(P<0.05). Conclusions:After the seizure, adenylate hydrolysis rate increased significantly, compared with patients with partial seizures, the increasing of adenylate hydrolysis rate of Comprehensive seizures is more obvious. It is prompt that the increasing of adenylyl cyclase activity might be involved in seizure termination mechanism.Chapter 2 The correlation between activity of serum soluble nucleotide phosphodiesterase activities and epilepsy of different seizure types Aim:To investigate the changes of serum soluble nucleotide phosphodiesterase activities after seizure in patients with epilepsy of different seizure types, in order to understand the role of soluble nucleotide phosphodiesterase activities in the seizure. Methods:From Mar 2014 to Dec 2015,65 patients with epilepsy in our hospital were enrolled in the treatment of epilepsy patients. At the same time, the collection routine physical examination of the normal staff of 35 cases as healthy control group. By Ultraviolet rays absorption spetrophotometry, the changes of phosphodiesterase levels, lactate dehydrogenase(LDH) level of 5 minute, 10 minute, 20 minute and 10 h in case group were observed, compared with normal control group; The changes of phosphodiesterase levels, lactate dehydrogenase(LDH) level of 5 minute, 10 minute, 20 minute and 10 h in comprehensive seizures were observed, compared with partial seizures. All data analysis used SPSS21.0 software package, P < 0.05, for the difference was statistically significant. Results:1.Patients in the interictal phosphodiesterase activity and control group no significant difference(P > 0.05);2.Episodes after 5min, 10 min, 20 min phosphodiesterase activity significantly increased. At 20 min after the onset of reached the peak, then decreased gradually, to attack after 10 h recovery complex to interictal levels(P<0.05).3. Comprehensive attack patients and partial seizures compared to attack after 5min, 10 min, 20 min phosphodiesterase activity significantly increased. At 20 min after the onset of peak, decreased gradually after, to attack after 10 h recovery to interictal levels(P<0.05);4.There was no significant difference in LDH activity between the changes of the time points and the time points after the onset of the seizures(P > 0.05). Conclusions:Phosphodiesterase activity was significantly after the seizure, phosphodiesterase activity increased more significantly after comprehensive seizures.phosphodiesterase activity is closely related to the increasing of ATP hydrolysis rate, It was further proved that the activity of adenine nucleotides increased significantly, which might be a regulation mechanism of the termination of seizures; Phosphodiesterase activity increased more significantly after a comprehensive seizure, it is more obvious confirmed that the effect of adenosine activity on the regulation of comprehensive seizures is stronger.Chapter 3 Adenosine A1 receptor on amygdala kindling damage mechanism of hippocampal neurons in epileptic rats Aim:To investigate the effects of adenosine A1 receptor activity of hippocampal neurons in epileptic rats kindled injury, and provide a theoretical basis for the treatment of epilepsy. Methods:1.84 SPF male Wistar rats were selected, according to the random number table method, the animals into normal group, induced epilepsy group, induced epilepsy + adenosine A1 R antagonist agent(8 cyclopenty- 1, 3-dipropylxanthine, DPCPX) group, induced epilepsy + adenosine A1 R agonist( 2-chloroadenosine, 2-CADO)4 groups(n = 21). Epilepsy group、epilepsy+DPCPX group、 epilepsy+2-CADO group by electrical stimulation of epileptic kindling model. The normal group without surgery and electrical stimulation induced epilepsy treatment; epileptic epileptic group model before and after the establishment of the success was not injected with any drug; successfully established after successful one hour before and 1 h tail intravenous injection of 0.3 mg / kg DPCPX caused by epilepsy +DPCPX group of rats epileptic model;epilepsy +2-CADO of epilepsy rats epileptic model 1 h before and 1 h tail intravenous injection of 0.6 mg / kg 2-CADO. By TUNEL methods, observed successfully established after 1 days, 15 days and 30 days in the CA3 region of the hippocampus pathological changes and neuronal apoptosis index changes in epileptic model., all data analysis used SPSS21.0. Results:1.Epileptic group, induced epilepsy+DPCPX group, induced epilepsy+2-CADO groups of animals in kindling epilepsy after 1 day, 15 days, 30 days showed varying degrees of neuronal cells arranged in a loose irregular, fuzzy contour, with unclear margin, atrophy of nucleus, cytoplasmic vacuoles neuron structure damage;2.At the same time, causing epilepsy+DPCPX structure of neuron damage degree with epilepsy group increased, induced epilepsy +2-CADO group with epilepsy group reduced. Normal group in the AI changes at different time points was not obvious(P > 0.05) and epileptic group, induced epilepsy group +DPCPX, induced epilepsy +2-CADO AI with prolonged seizure, the apoptosis index increased gradually(P < 0.05);3.At the same time, causing epilepsy group, epilepsy group+DPCPX, induced epilepsy +2-CADO AI were significantly higher than those in normal group(P < 0.05), induced epilepsy +DPCPX AI were significantly higher than that of epilepsy group(P < 0.05); induced epilepsy +2-CADO AI was significantly lower than that of epilepsy group and induced epilepsy +DPCPX group(P < 0.05). Conclusions:Seizures can cause neuronal injury and apoptosis,the activity of A1 R is decreased, and the injury and apoptosis of neurons is more obvious. This may be one of the mechanisms of neuronal injury after epilepsy; By increasing the activity of adenosine A1 R can protect neurons and reduce the damage, it may be a therapeutic direction for the termination of seizures.