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The Effect On Liver And Kidney Of Epileptic Rats Treated With Valproic Acid,Carbamazepine And Topiramate

Posted on:2009-06-02Degree:MasterType:Thesis
Country:ChinaCandidate:G L LiFull Text:PDF
GTID:2144360245484511Subject:Neurology
Abstract/Summary:PDF Full Text Request
Objective:Epilepsy is one of the common,chronic diseases with seizures in central nervous system.It is sudden,transient cerebral dysfunction caused by super synchronic and abnormal discharge of cerebral cells.So far as,antiepilepticdrugs (AEDs) are the major therapy of epilepsy mesonds.Some epileptics need to use AEDs long-time,even lifetime.The quality of life in epileptics is paid attention to.There are many factors which will affect the quality of life of patients with epilepsy, such as severity of the attack,seizure frequency,drug's adverse reac -tions. Both of drug's adverse reactions and seizure frequency are major factors in affecting the quality of life of patients with epilepsy.To reduce the occurrence of adverse reactions has become one of the most concerned issues in patients with epilepsy. This test is that liver, kidney dysfunction will be related of apoptosis in the course of taking anti-epileptic drugs. Apoptosis is one form of cell death. Apoptosis mainly concentrated in the Fas / FasL expression in the present study. Fas ligand (FasL) is a tumor necrosis factor (TNF)and Fas receptor (FasR) is and TNF receptor (TNFR) family,which are the protein molecules of cell-mediated apoptosis in cell surface by a film or a soluble form. 30 epilepsy model induced of pentylenetetrazole (PTZ) will be grouped separately five groups ,valproate (VPA) group (n=6),Carbamazepine (CBZ) group (n=6),topiramate (TPM) group(n=6),pentylenetetrazole (PTZ) group(n=6),saline (NS) group(n=6). The liver and kidney cell observed by HE staining in light; Fas and FasL expression observed by immunohistochemical, thereby liver and kidney dysfunction is related of apoptosis in course of antiepileptic drugs in the treatment of patients with epilepsy.Methods:1 Animal model of epilepsy: 35 healthy male 10 weeks Sprague-Dawley(SD) rats (weight 200±20g).Rats are given 1% pentylenetetrazole(PTZ) with intraperitoneal injection by 35 mg/kg·d and rats in control group are given equivalent saline in day .we can observe the changes in behavior,20 days later,according to Racine Classification Standard: 0: no reaction;1: Facial clonic, including the blink of an eye, to be dynamic, rhythmic chewing;2:a foundation of rhythm and nodded; 3:two plus forelimb clonic;4:3 and hindlimb stand up;5:four plus fall. Each of the animals who has already been three times in a rowⅡgrade level or aboveⅢgrade level were observed and recorded,the author believed to be fully lit.30 epilepsy animal modeles were divided into VPA group (n = 6),CBZ group (n = 6),the TPM group (n = 6),PTZ group (n = 6) and saline (n = 6), according to randomize method. The two rats who dead and three rats who fail the requirement of model in the process of modeling, be removed, ensure that each group have 6 animal.2 Drug therapy of epilepsy model: After rats are fully kindled,experimental group VPA group,CBZ group and the TPM group were given with 25 times drugs according to the standard weight of the adult average; PTZ group and NS group given 0.9% saline ,for 20 days. Observe model seizures in course of drug therapy.3 Preparation of samples: After one and half an hour infusion with 4% glutaraldehyde from the left ventricle , SD rat peritoneal ripped and cutted the left liver lobe,the left kidney by size 1 mm3 and quickly add to 4% of the fixative of polyfor- maldehyde,conventional biopsy done by HE staining and imm- unohistochemical technique after 24 hours paraffinembedd.4 HE staining: The cell morphology made by hematoxylin and eosin is observed in the light microscope.5 Immunohistochemistry techniques: After the paraffin sections,the antigen retrieval, goat serum closed,Fas and FasL polyclonal antibodies used,the second- antibody, third-antibody incubated,DAB color and observed under the microscope.Result:1 The control of epileptic rats given all kinds of antiepile- ptic drugs: The rats in every experiment had epilepsy attack of different degree of seizures. After intragastric handling,the group of experimental rats significantly reduce seizures,but PTZ group don't reduce and the saline group don't seizure. 2 HE staining: Observing morphological changes of liver and kidney celles in light microscope: liver cells in the periph- eral central zone and renal tubular cells can see vacuolar changes,glomerular mesangial matrix proliferation , thickening of the basement membrane and extracellular matrix accumula- tion, tubular arophy or mild luminal expansion, cell swelling, cytoplasmic vacuoles in the VPA group, the CBZ group, the TPM group .3 Immunohistochemistry3.1 The comparence with each group about Fas, FasL prot- ein expression in liver cells after drug intervention:The comparence of VPA group and TPM group were no significant differences (P>0.05)The comparence of VPA group and CBZ group,PTZ group and NS Group were significant differences (P<0.05)The comparence of TPM group and CBZ group,PTZ group,NS group were significant differences (P<0.05); The comparence of CBZ group,PTZ group and NS group were compared between,no significant difference (P>0.05).3.2 The comparence with each group about Fas, FasL prot- ein expression in renal cells after drug intervention:The comparence of VPA group and TPM group were no significant differences (P>0.05)The comparence of VPA group and CBZ group,PTZ group and NS Group were significant differences (P<0.05)The comparence of TPM group and CBZ group,PTZ group,NS group were significant differences (P<0.05);The comparence of CBZ group,PTZ group and NS group were compared between,no significant difference (P>0.05).Conclusion1 We can see that vacuolar changes in rat liver cells of the peripheral zone and renal tubular cells in valproate, topiramate group by HE staining.2 Using valproate and topiramate in epilepsy rats cause liver and kidney cell apoptosis,and the positive cell rate is higher than Carbamazepine,PTZ and control group .3 The abnormalities of liver and kidney in course of taking AEDs may be related to apoptosis.4 Fas / FasL system in the liver, kidney apoptosis play a role.
Keywords/Search Tags:anti-epileptic drugs, liver, kidney, apoptosis, Fas, FasL
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