Therapeutic Effect Of Epalrestat Combined With Beraprost Sodium On Diabetic Peripheral Neuropathy

Objective: To investigate the therapeutic effect of epalrestat combined with beraprost sodium on diabetic peripheral neuropathy(DPN).Methods: A total of 97 patients with DPN were randomly divided into epalrestat group(n=30),beraprost sodium group(n=32)and epalrestat combined with beraprost sodium group(n=35).After 12 weeks treatment,Blood glucose and lipid,total symptoms scores and median nerve,peroneal nerve motor conduction velocity and sensory conduction velocity were investigated in three groups.Results: 1.There was no significant difference in fasting blood glucose,triglyceride,total cholesterol,high density lipoprotein cholesterol,and low density lipoprotein cholesterol before and after treatment in the three groups(P>0.05).2.After treatment,the TSS scores of patients were declined(P<0.05),and combination group was lower than that of the epalrestat group and the beraprost sodium group(P<0.05).3.The nerve conduction velocity of the three groups was improved compared with before that treatment(P<0.05).With regard to nerve conduction velocity improvement in three groups,epalrestat combined with beraprost sodium group had more rapid velocity than the other two groups(P<0.05).Conclusion: Epalrestat combined with beraprost sodium in treatment of DPN could produce best therapeutic efficacy.Background: Diabetes mellitus is a chronic metabolic disease whose main pathogenesis is pancreatic b cells dysfunction and insulin resistance.In recent years,it has been found that lipopolysaccharide(LPS),a bacterial product of the intestine,is involved in the activation of chronic inflammation in type 2 diabetes.LPS,also known as endotoxin,is the main component of the cell wall of gram-negative bacteria and released after the bacteria break down.LPS activates downstream signaling pathways such as c-Jun NH2-terminal kinase(c-JNK)or NF-? B by binding to toll like receptor 4(TLR4),a specific receptor on the surface of immune cells,inducing a chronic inflammatory response and is associated with the occurrence of chronic metabolic diseases such as type 2 diabetes.The studies have shown that pancreatic ? cell membrane also exists TLR4,and LPS could damage ? cell by binding to TLR4.Type 2 diabetes mellitus is often complicated with lipid metabolism disorder,and lipotoxicity plays a key role in the pathogenesis of diabetes mellitus.Lipotoxicity refers to excessive lipids-mainly excessive free fatty acids deposit in non-adipose tissues(including pancreatic ? cell,skeletal muscles,liver tissue,etc.)and cause dysfunction.Palmitate(PA)is one of the important components of free fatty acids.Studies have shown that PA can induce apoptosis and inhibit the synthesis and secretion of insulin by activating endoplasmic reticulum stress,oxidative stress;on the other hand,it binds to TLR4 and damages ? cells by activating c-JNK or NF-? B.In recent years,the damage of LPS combined with PA on immune cells has been studied.However,whether affecting ? cells through TLR4 has not been reported.Therefore,this study was to observe the damage effect of LPS combined with PA on ? cell.Objective: To investigate the role and mechanism of lipopolysaccharide combined with palmitate in ? cell injury.Methods:(1)After rat insulinoma INS-1 cells were treated with various concentrations of LPS(10,50,100,200 and 500 ng/m L)for 24 h,cell viability of INS-1 cells were measured by MTT assay and the apoptosis of INS-1 cells were detected by Annexin V-FITC / PI double staining flow cytometry.(2)After INS-1 cells were treated with various concentrations of PA(0.1,0.2,0.3,0.4 and 0.5 m M)for 24 h,the cell viability of INS-1 cells were measured by MTT assay and the apoptosis of INS-1 cells were detected by Annexin V-FITC / PI double staining flow cytometry.(3)INS-1 cells were treated with PA(0.3m M)combined with LPS(50,100,200 and 500 ng/m L),cell viability was measured by MTT,and cell apoptosis was detected by Annexin V-FITC / PI double staining flow cytometry.(4)The expression of TLR4 and NCDase in INS-1 cells were determined by Western-blot after treatment with PA(0.3 m M)combined with LPS(200 ng/m L).Results:(1)The apoptosis and cell viability of INS-1 cells were not affected by different concentrations of LPS for 24 h.(2)INS-1 cells were stimulated with different concentrations of PA for 24 h,and cell viability of INS-1 cells began significantly to be inhibited at the concentration of 0.3m M PA.(3)INS-1 cells were treated with different concentrations of LPS combined with PA for 24 h,the apoptosis and viability of INS-1 cells were significantly affected by PA(0.3m M)combined with LPS(200ng/m L).(4)The expression of TLR4 increased and the NCDase decreased,after INS-1 cells were treated with PA(0.3m M)combined with LPS(200ng/m L)for 24 h.Conclusion: Lipopolysaccharide combined with palmitate damaging c cells may be related to the activation of TLR4 receptor and inhibition of NCDase activity.