| Background and Objectives The pathogenic factors of DPN were complicated,including oxidative stress,apoptosis,vascular and metabolic factors,as the key of three energy metabolism and the main source of reactive oxygen species,mitochondria was the target organ of oxidative damage and apoptosis,and played an important role in the process of insulin secretion,participated in diabetes and its complications,so it became one of the important mechanisms of DPN.As one of the basic events in cell,fusion and fission of mitochondria occured simultaneously and continuously,they kept a dynamic balance,and this balance was necessary to maintain morphology and function of mitochondrial,once the balance was broken,can lead to abnormal function.When Dynamin-related protein-1(Drp-1)was over expression,and mitochondrial fission is higher than fusion,it can break the dynamic balance,and lead to the change of mitochondrial structure and function,activation of apoptotic factors,thereby inducing apoptosis.It has been proved that Drp-1 can affect the morphology and function of mitochondria and promote apoptosis,which is closely related to diabetes,heart disease,tumor and neurodegenerative diseases.To explore the effectiveness of Mudan granule;and Mudan granule combined with alpha lipoic acid in the diagnosis and treatment of DPN and its mechanism.,we observed the relationship between Drp-1,Bax,Bcl-2 and DPN,and the effection of Mudan granule and Mudan granule combined with alpha lipoic acid on Drp-1,Bax,Bcl-2.Methods Choose the rats whose blood glucose is no less than16.7mmol/L in the model,from which 50 rats were chosen and randomly divided into four groups: diabetes mellitus group(DM),Mudan particles group(MD),α-lipoic acid groups(LA),combined treatment group(CT).Besides setting healthy rats as normal control(NC)group.The sciatic nerves conduction velocity(s NCV)was measured after drug treatment 12 weeks later,while antioxidant enzymes was examined with colorimetry.All the sciatic nerves of rats were observed by electron microscope and the ultrastructure of sciatic nerve in each group was observed by transmission electron microscope.The sciatic nerves of all the rats were separated,the removed nerves were used for detecting the expression of Drp-1、Bax and Bcl-1 m RNA by Real-time PCR.Result 1.Compared with NC group,the rats in DM group were listlessness,drinking and eating more,and bending arch back;their hairs were dirty and yellow,skin was cankered,activities were reduced,pads were wet,body weights grouped slowly even decreased,eye cataract was changed;The rats in the treatment group also had the symptoms,but were lighter than those in the DM group.During the course of the experiment,4 rats were dead,there were 2 deaths in the DM group,1 deaths in the MD group and 1 deaths in the LA group.2.The blood glucose levels of NC、DM、MD、LA and CT groups before modeling were 6.07±0.45、6.09±0.38、6.10±0.49、6.22±0.39、6.22±0.40 mmol/L,after 4 weeks of treatment,they were6.12±0.16、27.10±1.13、28.27±1.44、26.37±1.33、25.32±1.25 mmol/L,after 8 weeks of treatment,they were 5.87±0.26、27.16±3.30、28.23±3.62、26.43±3.21、25.50±3.03 mmol/L,after 12 weeks of treatment,they were 6.17±0.29、27.41±3.07、28.58±3.29、26.70±3.24、25.73±3.00 mmol/L..3.s NCV of NC、DM、MD、LA and CT groups was 55.76±0.60、43.39±1.35、49.11±0.55、49.07±0.51、52.38±0.75 m/s.4.The levels of T-SOD(U/ml)in NC、DM、MD、LA and CT groups were 248.04±22.13、99.84±5.81、160.89±11.63、154.09±15.79、175.79±8.64;the levels of MDA(nmol/ml)were 4.17±0.28、8.66±0.78、6.26±0.17、6.10±0.20、5.21±0.36;the levels of CAT(nmol/ml)were 14.99±1.08、7.97±0.91、9.70±0.44、9.86±0.34、11.83±0.51;the levels of GSH(mg/L)were 19.73±1.41、7.50±0.65、11.99±0.81、11.57±0.89、14.82±1.22。 5.In the NC group,the myelinated nerve fibers in the sciatic nerve of rats were dense and compact,and the mitochondria arranged uniformly,Schwann was normal;In the DM group,the myelin sheath of the myelinated nerve fibers was isolated,some of them appeared demyelination,mitochondria swelled and deformed,the cristae was disappeared,and the Schwann was necrosis;in the MD group,the sciatic nerve showed no obvious changes of myelin sheath,and the changes of myelin sheath were lighter than that of the DM group;In the CT group,the sciatic nerve was rich and abundant in myelinated fibers,the myelin sheath was loose,the Schwann cells were mildly edematous,and most of the mitochondria were normal.6.The expressions of Drp-1m RNA were(0.99±0.07)、(1.78±0.08)、(1.48±0.09)、(1.44±0.10)、(1.30±0.05)in NC、DM、MD、LA、CTgroup;the expressions of Bax m RNA were 为(1.09±0.21)、(7.08±0.86)、(4.95±0.83)、(4.52±0.88)、(2.86±0.54);and the expressions of Bcl-2 m RNA were(7.80±0.40)、(2.99±0.64)、(4.06±0.81)、(4.09±0.80)、(5.62±0.83).Conclusion 1.After 12 weeks of continuous hyperglycemia in diabetic rats,it is considered to be DPN.2.The over-expression of Drp-1 leads to mitochondrial dysfunction,it can promote the onset of DPN.3.Mudan granule can reduce the expression of the Drp-1,and reduce cell apoptosis and oxidative stress level,it also has certain protective effect on sciatic nerve in diabetic rats... |
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