| Purpose: The purpose of this study is to explore the best initial treatment time of Mudan Granule in preventing and treating diabetic peripheral neuropathy.To observe the effects of different initial treatment time on general state,blood glucose,body weight,hot pain threshold,nerve conduction velocity,sciatic nerve morphology and epidermal fiber density of diabetic rats.It provides an experimental theoretical basis for the best starting time of clinical medication of Mudan Granules.Material and method:Sixty SPF SD healthy male rats,weighing 230-270 g,were randomly selected as normal control group after 7 days of adaptive feeding.After fasting for12 hours,the remaining 50 rats were given 1%STZ solution(STZ)prepared with 0.1 mol/L citrate buffer at PH4.2(ratio: 53 mg/kg)After 72 hours,rats with fasting blood glucose?16.7mmol/L were randomly divided into STZ model group,0w intragastric group,2w intragastric group,4w intragastric group and 6w intragastric group.There was no intervention of traditional Chinese medicine in STZ model group,and the other four groups were given Mudan granules by gavage at 0w,2w,4w and 6w respectively until the end of 8w after the model was established.At the end of 8 weeks,the changes of general state,blood sugar,body weight,latent period of foot contraction and motor nerve conduction velocity were observed.The morphology of nerve fibers,myelin sheath and axon were observed,and the effect of Mudan Granule on epidermal fiber density of diabetic rats was detected by immunohistochemistry.Results:1.Rats in normal control group have normal demeanor,bright fur color,high body weight,quick response and free movement.In STZ model group,rats were listless,slow in activity and reaction,dull in fur,increased in food intake,water consumption and urine output,and decreased in weight.The other treatment groups had the above symptoms,but compared with STZ model,the symptoms improved.Moreover,the general state of rats in 0w and 2w gavage groups improved most significantly.2.Compared with the normal control group,the blood glucose concentration in 2.STZ model group and each intragastric group increased significantly(P < 0.01).Compared with STZ model group,there was no statistical difference in blood glucose between intragastric administration group and STZ model group(P > 0.05).3.Compared with normal control group,the weight of diabetic rats in each group decreased significantly(P < 0.01).There is a statistical difference in body weight between the gavage group and the STZ model group(P<0.05),and there is a significant statistical difference between the 0w gavage group and the STZ model group(P < 0.01).4.Compared with the normal control group,the nerve conduction velocity of diabetic rats in each group decreased significantly(P < 0.01).Compared with STZ model group,the nerve conduction velocity of each intragastric group increased significantly(P < 0.01),among which the nerve conduction velocity of 0w,2w and 4w intragastric groups increased significantly(P<0.05).The nerve conduction velocity in 0w group was significantly higher than that in 2w and 4w groups(P<0.01),2w group was significantly higher than that in 6w group(P < 0.01),2w group was higher than that in 4w group(P < 0.05)5.Compared with STZ model group,the latent period of heat-shrinkable foot in diabetic model rats and normal control group was significantly shortened(P<0.01).Compared with STZ model group,the latent period of heat-shrinkable foot in all groups was significantly prolonged(P < 0.05),among which the latent period of heat-shrinkable foot in 0w,2w and 4w groups was significantly prolonged(P < 0.01).Compared with each treatment group,the latent period of heat-shrinkable foot in 0w group and 2w,4w and 6w group was significantly prolonged(P < 0.01).Compared with the 4-week and 6-week groups,the latent period of heat-shrinkable foot in the 2-week group was significantly longer(P < 0.01).Compared with the 6-week group,the latent period of heat-shrinkable foot in the 4-week group was relatively longer(P < 0.05).6.In the normal control group,nerve fibers were normal,distributed evenly and densely,myelin sheath stained evenly,and axons were clear.In STZ model group,nerve fibers were loosely listed,myelin sheath swelled unevenly,thinned and even demyelinated.However,nerve fiber injury was improved in the intragastric group.In addition,the improvement was the most significant in 0w and 2w groups,and the nerve fibers were arranged neatly and the staining density was uniform.7.Compared with the normal control group,STZ model group and each intragastric group have significantly lower epidermal fiber density(P<0.01).Compared with STZ model group,each intragastric group has significantly higher epidermal fiber density(P < 0.01)The epidermal fiber density of 0w group was significantly higher than that of 2w,4w and 6w group(P<0.01),2w group was significantly higher than that of 4w and 6w group(P < 0.01),and 4w group was higher than that of 6w group(P < 0.01).Conclusion:After successful establishment of diabetic model rats,Mudan Granule can improve motor nerve conduction velocity,latency of hot pain threshold response,pathological morphology of sciatic nerve and density of epidermal nerve fibers in diabetic rats at different starting times,and the earlier the starting time,the more obvious the improvement of latency of hot pain threshold response in diabetic rats.Therefore,the application of Mudan granules in the early stage of diabetes is helpful to delay the occurrence of diabetic peripheral diseases. |
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