| Purpose:Based on the theory of microcirculation disturbance,this study observed the changes of microcirculation blood flow of lower limbs,peripheral nerve conduction velocity,sciatic nerve morphology and structure,and the content of endothelin in serum of diabetes rats after intervention with Mudan granule at different stages,and discussed the role of microcirculation disturbance in diabetes peripheral neuropathy,To provide a theoretical basis for determining the best time for Mudan granule to prevent and treat diabetes peripheral neuropathy.Material and method: 60 SPF healthy male SD rats weighing 230-270 g were randomly selected.After 7 days of adaptive feeding,10 SD rats with normal blood glucose were randomly selected as the normal control group.After fasting for 12 hours before modeling,the other 50 rats were injected with 1% STZ solution according to 50 mg / kg left lower abdomen,and fed with water 30 minutes after injection.After 72 hours,tail vein blood was taken to detect fasting blood glucose.If fasting blood glucose ≥ 16.7 mmol / L,the modeling was considered successful,and those that did not meet the standard were excluded.After modeling,50 successful rats were randomly divided into STZ model group,0 w gavage group,2 W gavage group,4 W gavage group and 6 W gavage group,with 10 rats in each group.The STZ model group was given the same dose of normal saline from 0W,the 0W gavage group was given immediately after modeling,and the other three groups were given Mudan granules by gavage at 2W,4W and 6W respectively.The four groups were fed continuously by gavage and free diet and drinking water until 8W after modeling.After 8W,the changes of general state,blood glucose,body weight and nerve conduction velocity were observed,and the changes of microcirculatory blood flow of rat lower limbs were measured by laser Doppler flowmetry.The materials were taken under anesthesia.The changes of serum endothelin content were detected by ELISA,and the morphological changes of sciatic nerve fibers,axons and myelin sheath were observed.Results:1.During the whole experiment,it can be observed that the rats in the normal control group have good mental state,shiny hair color,sensitive response,continuous weight growth and no symptoms of "more than three and less";STZ model group rats were depressed,grew slowly,their hair color was dull,dull,slow in response,slow in action,increased significantly in food intake,drinking water and urine volume,and increased slowly in weight;The above symptoms of rats in 0Wgavage group,2W gavage group,4W gavage group and 6W gavage group were alleviated in varing degrees,and the general state was better than that in STZ model group,among which the state of rats in 0W gavage group and 2Wgavage group was better;2.During the experiment,the blood glucose of rats in the normal control group remained at a normal level,while the blood glucose of rats in each group remained at a high level after modeling.After modeling,the initial blood glucose and blood glucose after 8W in each group were significantly higher than those in the normal control group,which was 5 times higher than that in the normal control group,and the difference was statistically significant(P<0.01);There was no significant difference between each gavage group and STZ model group(P >0.05);3.After modeling,the body weight of rats in each group was significantly lower than that of normal control group(P<0.01).There was no significant difference in initial body weight between 0W,2W,4W and 6W gavage group and STZ model group(P>0.05);After 8W,there was significant difference between 0W,2W,4W and 6W gavage group and STZ model group(P<0.05);There was significant difference between 0W gavage group and STZ model group(P<0.01);4.After modeling,the nerve conduction velocity of rats in each group decreased significantly compared with the normal control group(P<0.01);The nerve conduction velocity of each gavage group was significantly higher than that of STZ model group(P<0.01);Compared with2 W and 4W,6W gavage groups,the nerve velocity of 0W gavage group was significantly higher than that of 4W gavage group(P<0.01);the nerve conduction velocity of 2W gavage group was relatively higher than that of 4W gavage group(P< 0.05);the nerve conduction velocity of 2W gavage group was significantly higher than that of 6W gavage group(P<0.01),and the nerve conduction velocity of 4W gavage group was significantly higher than that of 6W gavage group,nerve conduction velocity increased significantly(P<0.01)5.After modeling,the lower limb microcirculatory blood flow of rats in each group decreased significantly(P< 0.01);Compared with STZ model group,the lower limb microcirculatory blood flow of rats in each gavage group increased,and the lower limb microcirculatory blood flow of rats in 0w,2W and 4W gavage group increased significantly compared with STZ model group(P<0.01);Compared with the treatment groups,the earlier the time of gavage;the higher the blood flow of lower limb microcirculation of rats(P<0.01);6.ELISA showed that the content of ET in serum of rats after modeling was significantly higher than that of normal control group(P<0.01);The content of ET in serum of rats in0 W,2W and 4W gavage group was significantly lower than that in STZ model group(P<0.01);and the content of ET in serum of rats in 6W gavage group was relatively lower than that in STZ model group(P<0.05);Compared with 4W and 6W gavage groups,the content of ET in serum decreased in 0W gavage group(P< 0.05,P < 0.01);The content of ET in serum of 2W gavage group was significantly lower than that of 6W gavage group(P < 0.01);The content of ET in serum of 4W gavage group was lower tahn that of 6W gavage group(P <0.05);7.In the normal control group,the nerve fiber cells of rats were normal in size,evenly distributed,evenly stained in myelin sheath,the axons in myelin sheath were clearly visible,and there was no swelling and atrophy of axons;In STZ model group,the arrangement of nerve fiber cells was loose,the myelin sheath swelled unevenly,thinned,and even demyelinated in part,and the axon changed significantly;Compared with STZ model group,the injury of sciatic nerve fibers in 0W,2W,4W and 6W gavage groups was improved in varying degrees.Among them,the improvement of sciatic nerve fibers in 0W and 2W gavage groups was the most obvious,and the nerve fibers were arranged neatly and stained evenly.Conclusion:After the application of Mudan granule,the lower limb microcirculation blood flow of diabetes rats can be improved.The earlier the starting time of medication,the more significantly the lower limb microcirculation blood flow is increased.At the same time,the nerve conduction velocity,the morphological structure of sciatic nerve and the content of endothelin in serum are improved.To some extent,the effect of Mudan granule in preventing and treating diabetes peripheral neuropathy may be achieved by improving microcirculation disturbance.Therefore,the application of Mudan granule in the early stage of diabetes can help to improve microcirculation disorders,prevent and delay the progress of peripheral neuropathy in diabetes. |
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