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The Pathogenesis Of Peripheral Nerve And Retinopathy In Diabetic Rats And Protective Effects Of Batroxobin

Posted on:2007-05-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y S WangFull Text:PDF
GTID:1104360185954864Subject:Neurology
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Objective Diabetic peripheral neuropathy and retinopathy are thecommon chronic complications of diabetes mellitus,which have becomethe important reasons of diabetic patients crippled.However,the specialeffective methods of treatment are not available at present,therefore,it isvery helpful to discuss thoroughly the pathogenesis of DPN and DR. Themultitudinous research indicated that the many kinds of nerve nutritionfactor possibly participate in the pathogenesis of DPN and DR.Thisresearch first establishes stably,reliable animal diabetes model,thenobserves the pathology changes of the sciatic nerve and retina andexamines the peripheral nerve conduction speed and the bloodrheology.At the same time,we measure the level of various nervesnutrition factor before and after the treatment of Batroxobin in the sciaticnerve and retina of big mouse through the immunohistochemistry and thehome position hybrid method so as to provide the new rake spot of thetreatment of DPN and DR.Methods Wistar rats were used. Diabetes was induced by singleintraperitoneal injection of Streptozocin (55mg/kg body weight) randomlychosen from the total group. The residual six mice received an equalvolume of citric acid buffer as nondiabetic control (N). 48 hours later,ratswith plasma glucose concentration>16.7 mmol/L were selected anddivided at random into five groups: diabetic rats (D1,D2) and diabeticrats treated with Batroxobin (T1,T2). T1 feeded in 8 weeks and T2 feededin 12 weeks were given Batroxobin injection (8BU/kg body weight)dissolved in distillation water by gavage once a day. Residual groupsreceived the distillation water only. Body weight and blood glucose weremeasured monthly. After 2 months,motor nerve conductionvelocity(MNCV) and sensory nerve conduction velocity (SNCV) were determinedin sciatic-tibial nerve conducting system. After that,blood from eachgroup was obtained to measure blood and plasma viscosity and thensciatic nerves and eyeballs of all the rats were extirpated. Semithin andultrathin cross sections were obtained and used for morphologicalobservation.At last,the levels of NGF,IGF-1,VEGF and bFGF weremeasured in the sciatic nerve and retina of all the rats through theimmunohisto-chemistry and the home position hybrid methods.Results The body weight of D1,D2 and T1,T2 rats weresignificantly reduced (P<0.05,vs N). Plasma glucose concentrations indiabetic rats were significantly higher than that of N rats (P<0.05). Therewere no significant effects of Baxobin on the bodyweight and plasmaglucose level in diabetic rats. Sciatic SNCV and MNCV were significantlyslowed and the blood and plasma viscosity was significantly increased inD1 and D2 rats (P<0.05,vs N). Treatment with Baxobin thoroughlyprevented the slowing of SNCV and MNCV and the decrease of the bloodand plasma viscosity in diabetic rats (P<0.05). Light and electronmicrographs in D1 and D2 rats showed serious loss of demyelination andthe lesion of retinae and the treatment rats showed moderate improvement.On the other hand,N rats had mild or micro lesions perhaps due toartifactors. The expression levels of NGF,IGF-1,VEGF and bFGF wereinduced in the sciatic nerve of all the rats revealed by theimmunohistochemistry method.On the contrary,those in retina wereincreased except the reduced expression of NGF.Batroxobin can suppressthe changes in the sciatic nerves and retinae (P<0.05),in which only theexpression level of IGF-1 in the sciatic nerves was no difference. Thehome position hybrid analysis was in agreement with theimmunohistochemistry results.Conclusions Single intraperitoneal injection of Streptozocin mayestablish the stable and reliable experimental DPN animal model andobviously similar to human diabetes retina early pathologicalchange.NGF,IGF-1,VEGF and bFGF play an important role in thepathogenesis of DPN and DR.Treatment with Batroxobin is beneficial inthe prevention of DPN and DR,possibly through the improvement ofblood rheology and the regulation of the expression level of NGF,IGF-1,VEGF and bFGF in the sciatic nerves and retinae.
Keywords/Search Tags:Diabetic peripheral neuropathy, Diabetic etinopathy, NGF, IGF-1, VEGF, bFGF, Batroxobin, Experimental study
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