Effects And Study Of Mechanism Of Angiotensin-Converting Enzyme Inhibitor On Diabetic Peripheral Neuropathy

Objective Diabetic peripheral neuropathy(DPN) is one of the most commonchronic complications of diabetes mellitus(DM).The pathogenesis of DPN remainsunresolved and safety and effective management is lacking in clinic.We can notimprove clinical symptom of patients even though the blood sugar is controlledstrictly. Although aldose reductase inhibitors, antioxidant agent, advanced glycationend products inhibition and vitamins gain some effects in animal experiments, but nosatisfactory effects in clinical application. ACE inhibitor as a vasodilator agent, canregulate confused haemodynamics and blood vessel active factors, improve themetabolism and blood flowing of nerve tissue.The aim of this study is to investigatethe prevention and therapy effects of ACEI on experimental DPN in the earlierstage,to observe the changes of oxidative stress indexes(SOD, MDA), Na~+K~+-ATPaseactivity and NF, MBP expression and capillary density of endoneurium in sciaticnerve and NO, NOS level in plasma and the effects of ACEI on these indexes, toexplore the mechanism of ACEI preventing and improving DPN in earlier periodfrom the theories of regulating metabolism disorder and improving nerve bloodflowing.Methods Diabetes was induced by streptozotocin(STZ).We determined nerveconduction velocity,thermal pain threshold, morphology changes of sciatic nerve andquantitative analysis of sural nerve of diabetic model group and normal control groupafter 2 weeks, 4 weeks, 6 weeks, 8 weeks, 12 weeks respectively,and observeddynamicly functional and morphologic changes of peripheral nerve of diabeticrats, established experimental DPN model, understood the development of nerve injury;Groupl was a prevention protocol,treatment was initiated immediately after verification of diabetes.Group2 was a intervention protocol,treatment was initiatedafter 4 weeks of of untreated diabetes.Each of two groups of rats Contained a set ofdiabetic model group,normal control group and diabetic rats treated with lisinopril,anACE inhibitor.After 8 weeks,we killed rats and observed blood sugur,body weight,nerve conduction velocity,thermal pain threshold,morphology changes of sciaticnerve and capillary,quantitative analysis of sural nerve in order to identify the effectsof lisinopril on experimental DPN in different periods;After isolating sciatic nerve,wedetermined SOD, MDA, Na~+K~+-ATPase activity in sciatic nerve and NO,NOS levelin plasma by spectrophotometry,assessed NF,MBP and capillary density of sciaticnerve by immunostraining in order to approach the mechanism of ACEI on DPN.Results After 2 weeks,diabetic rats showed slowing of motor and sensory nerveconduction velocities,lowering of thermal pain threshold.After 4 weeks,changes ofpathology of sciatic nerve were observed.With the duration extending,the functionaland structural damages of nerve were aggravated gradually;After 8 weeks oflisinoprilprevention or intervention treatment,nerve conduction velocity,thermal painthreshold,average section area of myelinated nerve fibers and capillary density ofendoneurium were changed,structural process of nerve tissue were delayed;Lisinoprilimprove nerve structure and function through several mechanisms includingimproving oxidative stress state,increasing NO,NOS level, Na~+K~+-ATPaseactivity,NF,MBP expression and capillary density of endoneurium.Correlationanalysis demonstrated, Na~+K~+-ATPase activity and capillary density of endoneuriumwas positive correlation with nerve conduction velocity.Conclusion 1.Neuropathy appear in earlier stage on experimental diabetic ratsand aggravate gradually with the duration extending.2.Lisinopril can improve nervefunction and structure at different degrees through prevention or interventiontreatment,but there are better effects by prevention treatment.3.Decreasing of bloodflowing and oxidative stress are the important factors of DPN.Lisinopril can improvenerve blood flowing and metabolic dysfunction by multilink and multitarget.ACEinhibitors are effective measurement on DPN.