Effect And Mechanism Of Pulse - Pass On Prevention And Repair Of Diabetic Vascular Endothelial Injury

Objective:The paper presents the study on the preventive and reparative effect and mechanism of the compound formula Maitongfang towards the diabetic vascular endothelium impairment through various stages of the different types of diabetic animal models. Methods:Four animal models are applied in the study known as Wistar rats fed by high sugar, high fat and high cholesterol feeding stuff, alloxan induced Wistar rats, GK rats and ob/ob male mice which simulate the early stage of diabetes, type1diabetes, type2diabetes, obese type2diabetes with insulin resistance respectively. The four animal models are applied with Chinese Medicine formula Maitongfang to prevent and treat with overall observation on the blood glucose, cholesterol, triglycerides, high-density lipoprotein, LDL, glycated LDL, lipoprotein (a), fasting plasma insulin, plasma TXB2, plasma6-Keto-PGF1α, monoxide nitrogen, endothelin, vascular endothelial growth factor, interleukin-6, biopsy of the femoral artery, renal biopsy and other indicators of the effects of animal experiments. Results:Maitongfang on the role of early stage of diabetic animal models:1. CM group compared to the model group had significant reduction of blood glucose.2. CM group compared to the model group significantly increased serum insulin levels.3. CM group compared to the model group reduced serum total cholesterol, triglycerides, lipoprotein (a) levels and increased HDL-C levels regulates abnormal lipid metabolism.4. CM group compared to the model group significantly increased NO content and moderately lowered ET levels to protect the normal function of the vascular endothelium.5.The vascular tissue morphology shows the CM significantly inhibited the femoral artery vascular endothelial cell injury and subendothelial edema and prevent the formation and deposition of lipid from penetrating further. Advanced application of Chinese Medicine Maitongfang, CM group of rats indicates to be significantly superior to other groups, vascular endothelial injury was significantly lighter. Maitongfang on the role of type1diabetic animal models:1. CM low-dose group compared with the model group had significantly lower blood sugar levels.2. CM low-dose group compared with the model group had significantly elevated serum insulin levels.3. CM group compared to the model group, TC, TG level decreased significantly and lower than the cilostazol group.4. CM high-dose group and cilostazol group significantly reduced TXB2compared to the model group;6-Keto-PGF1α in cilostazol group was significantly elevated compared to model group.5. CM high-dose group compared to the model group ET significantly reduced NO significantly increased NO increased cilostazol group compared with the model group.6.CM high-dose group had significantly inhibition on vascular tissue morphology of femoral artery with minor vascular endothelial cell injury and subendothelial edema. Maitongfang on the role of GK rats with type2diabetes:1.CM low-dose group showed significant hypoglycemic effect, the CM high-dose group had better effect than the rosiglitazone group.2. Serum insulin in CM high-dose group and rosiglitazone group had no significant difference; rosiglitazone group had lower insulin level than the CM low-dose group.3. Vascular endothelial growth factor in each group were significantly lower than the model group, CM low-dose group was significantly lower than the cilostazol group.4. Serum interleukin in CM high-dose and low-dose group were lower than the model group, cilostazol group lower than in the model group.5.Tumor necrosis factor in each group were lower than the model group; CM high-dose and low-dose group compared with the model group were significantly different compared with Western medicine two groups also have differences, suggesting that Chinese Medicine has significantly reduced serum tumor necrosis factor-a of spontaneous diabetic rats, but no dose-related significance.6. in terms of area, endothelial cell biopsy on average shows CM high-dose group had a focal area of less than30%; CM low-dose group showed multiple off a large area of about75%; cilostazol group rosiglitazone group, approximately60%; the model group set off an area of more than80%. Chinese Medicine has exact protective effect for endothelial. In this stage CM high-dose group has significantly protective effect on the vascular endothelial of type2diabetic rats. Maitongfang on the role of obese type2diabetes male mice with insulin resistance:1. Chinese Medicine had certain impact on the ingestion; especially the CM high-dose group was most obvious.2. Chinese Medicine improved glucose tolerance in mice to a certain extent, the effect of the CM high-dose group and middle-dose group was significantly higher than the low-dose group.3. Insulin sensitivity of model group reduced in8weeks, the insulin-sensitizing effect of Chinese Medicine is not obvious.4. Glucose tolerance in CM groups appeared to improve in12weeks, consistent with the results of8weeks, CM showed a hypoglycemic effect; significant hypoglycemic effect showed in rosiglitazone group.5. Insulin sensitivity model group decreased in12weeks, no significant insulin sensitivity improvement in peripheral tissue in the CM group.6.Glucose level in CM middle-dose and high-dose groups were equal to normal group, similar to the effect of rosiglitazone group and showed good hypoglycemic effect; CM groups had slight decrease in the content of LDL lipids compared to the model group; rosiglitazone group had high ALT levels to tell rosiglitazone had great damage to the liver, while the CM group also has over normal range ALT levels.7. Histological analysis showed steatosis and fat deposition phenomenon has been significantly improved in CM group compared to the model group, ballooning degeneration was reduced, Chinese Medicine can reduce the accumulation of fat in the liver. Conclusion:Maitongfang plays significant role in prevention and reparation of diabetic vascular endothelial impairment not only for diabetic animal model in early state, and also for animal model of type1diabetes and type2diabetes. The corresponding mechanism is achieved through regulating the state of hyperglycemia, protecting the morphology and function of vascular endothelium, adjusting lipid metabolism disorders, improving insulin secretion and insulin resistance, clearing radical scavenging, balancing vasomotor factors, inhibiting platelet aggregation, regulating the expression of angiogenic factors, protecting the integrity of the ultrastructure of the cell. Through early intervention, the incidence of diabetic vascular endothelial impairment can significantly reduce, suggesting the necessity of early application of Maitongfang. In molecular biology, Maitongfang may act through the key link PKC-ERK signaling pathways to produce the multi-point integrative and regulative effect for diabetic vascular endothelial impairment.