Study On Protective Mechanism Of Danzhijiangtang Capsule On Endothelial Dysfunction Of Diabetic Vascular Disease Based On VEGF/Akt/eNOS Signal Pathway

Objective Base on the role of VEGF/Akt/e NOS pathway in the pathogenesis of lower extremity vascular disease in type 2 diabetic patients and the effects of Danzhi Jiangtang Capsule on vascular endothelial injury,to investigate the mechanism of DJC promoting angiogenesis in diabetic vascular endothelial injury.Methods 1.Clinical StudiesA totall of 60 T2 DM patients with lower extremity vascular disease were divided into the control group and the treatment group with 30 cases in each group.All patients were given medicine hypoglycemic,lipid-lowering therapy combined with lifestyle intervention,the treatment group was treated with DJC,the control group was treated with DJC mimetic for one year.Observed in patients before and after treatment of symptom scores,FPG,2h PG,Hb A1 c,TC,TG,LDL-C,HDL-C,serum VEGF,e NOS,ABI levels,and calculate the total efficiency changes.2 Experimental StudiesA total of 60 male GK rats were fed for 1 weeks,10 rats were randomly selected as control group and the other 60 rats as model group,blank group were fed with normal diet,the rest 50 rats with 2% pentobarbital anesthetized with intraperitoneal 50mg/kg,ligation of the left femoral artery and its branches for amputation,built acute left lower limb ischemia model,finally successful model 49,9 rats were randomly divided into model group.There were 10 rats in pioglitazone group,DJC low,medium and high dose group.The control group and model group with normal saline for 12 weeks.The blood glucose,glycosylated hemoglobin,TG,TC,LDL-C,serum VEGF levels and the expression levels of VEGF,Akt and e NOS in ischemic tissues were observed in each group of rats.Result 1 Clinical study resultsAfter treatment,in the control group the total efficiency is 72.41%,89.59% in the treatment group,which is more efficiency(P<0.05);Both groups of TCM syndrome score are decreased significantly compared with before treatment(P<0.05),the treatment group is lower than the control group(P<0.05);Both groups of FPG,2h PG and Hb A1 c levels decrease after treatment(P<0.05),the treatment group is lower than the control group(P>0.05);Levels of TG,TC and LDL-C is decreased after be treated(P<0.05),while HDL-C level is increased(P<0.05);and the levels of TG,TC,LDL-C levels is lower than the control group,but the level of HDL-C is higher than the control group(P<0.05);Both groups serum VEGF and e NOS is decreased after treatment(P<0.05),serum VEGF,e NOS levels is lower than the control group(P<0.05);In both groups the patients with ankle brachial index were improved,but the control group is not significantly improved.2 Experimental resultsAfter 12 weeks of intervention treatment,The blood glucose and glycosylated hemoglobin levels in the blank group and saline group were higher than those in the western medicine group and DJC group(P<0.05).There was no significant difference between DJC groups and Western medicine group(P>0.05).The levels of TC,TG and LDL-C in the blank group and saline group were higher than those in the western medicine group and DJC groups(P<0.05).There was no significant difference between DJC groups and Western medicine group(P>0.05).The levels of HDL-C in blank group and saline group were lower than those in western medicine group and DJC groups(P<0.05).There was no significant difference between DJC groups and Western medicine group(P>0.05).The serum VEGF level in the saline group was higher than that in the blank group(P<0.05);the serum VEGF level in the western medicine group and the DJC group was lower than that in the normal saline group(P<0.05).DJC middle dose group was lower than that in the western medicine group(P<0.05).Detection results of Western blot protein,The relative expression of VEGF,Akt and e NOS protein in the left gastrocnemius muscle in the saline group was higher than that in the blank group(P<0.05);The relative expression of VEGF,Akt and e NOS protein in the gastrocnemius muscle of the western medicine group and DJC groups was lower than that of the normal saline group(P<0.05).Conclusion DJC promotes the repair of endothelial injury in diabetic vascular disease,improving the clinical symptoms and TCM syndrome scores of T2 DM patients with lower extremity vascular disease,reducing blood glucose and blood lipid level,downing regulation of serum VEGF level;inhibition of activation of VEGF/Akt/e NOS signaling pathway in ischemic tissue,promoting the repair of ischemic injury.