The Effection Of C Type Natriuretic Peptide In Femoral Aterry Stenosis Of Experimental Diabetic Rabbits

Background:In recent years, with changes in lifestyle and the aging of the population and other factors, The incidence rate of diabetes is increasing year by year. According to the Ministry of Health statistics in 2006, the prevalence rate of diabetes achieved 3 percent in our country, and was expected patients with diabetes be 4.23 million in 2030 in China^[1]. 80% diabetic patients died of vascular complication. Lower extremity vascular disease is one of the four major diabetes complications, 8% of the patients had been existence of lower extremity arterial disease when they were diagnosed as diabetic^[2], and the terminal low limb deformity rate of was 38%. There are many different treatments for low limb vascular disease. With the property of little damage, safty and effici ency, Percutaneous Transluminal Angioplasty is commonly in the diabetic vassal rebuild treatment. But, after the incidence of restenosis remains high, especially in diabetic lower extremity vascular occlusive disease of restenosis after PTA incidence as high as more than 30%.It is necessary for studying and resolving this issue to establish animal model of diabetes lower extremity artery stenosis. However, there is less report about animal m odel. At present, establishing lower extremity artery stenosis only uses mice or rabbit. But more of models can be used by rabbit, because the artery pathological change of rabbit endodermis stripping technique is similar with post-PTA restenosis of patient.The mechanism of restenosis do not illuminate by researcher up to now. Party of study about smooth muscle cell (SMC) proliferation and blood vessel remodeling demonstrated that it is important for post surgery restenosis. C type natriuretic peptide (CNP) which was mainly secreted by vascular endothelial cell. It could inhibit SMC proliferation and migration. It participated the vascular remodeling through autocrine and paracrine secretion. But, that CNP played the role in post-PTA restenosis is not demonstrated. In this study, the type 1 diabetes rabbit model is induced by tetraoxypyrimidine. And then, diabetes rabbit femoral artery sacculus proprius injured model was established through the saphenous artery. Blood plasma CNP and CRP density dy namic changes can be observed. The effect of exogenous CNP on endangium thickness degree can be observed simultaneously. Through all of the data, the role of CNP in diabetic rabbit extremity artery post-PTA restenosis can be explanation.Objective:1. To elucidate the methods of stenosis model set through balloon injured femoral artery on diabetic rabbits.2. To observe the dynamic changes of C type natriuretic peptide(CNP) and C reaction protein(CRP)in plasma and the preventive effect of exogenous CNP on vascular stenosis in a diabetic rabbit model after femoral artery injury.Methods:1. Setting up an animal model of diabetic rabbits with Alloxan in vine.2 After setting up an animal model of diabetic, the rabbits were divided into operation group (group A), control group (group B) and CNP treatment group (group C). Their femoral arteries were injured by balloon dilation through saphenous artery in Group A and C; group B was pseudo-operation group; group C was treated group by CNP. All groups gave normal feeding. Killed all the rabbits after 4 weeks and observed vascular stenosis under microscopeafter HE staining. Analysis the changes of intima media and lumen area between 3 groups. Determine the plasma concentration of CNP in group A & B, CRP in 3 groups. The statistical analysis was done by One way ANOVA and Student-Newman-keuls' q-test.Results:1. The operations on all the rabbits were finished successfully, during which 24 survived to the end of the experiment and the mean time for operation was (26±7) minutes. Vascular stenosis models were successfully obtained. The mean stenosis rate was (89.83±0.63)%.2. Compared with B group and C group, media area in A group were significantly increased, (0.28±0.18vs0.14±0.09 mm², P＜0.01; 0.28±0.18vs0.13±0.03mm², P<0.01). Intima area in A group were significantly increased, compared with B group and C group (0.14±0.05 vs 0.06±0.03mm²; 0.14±0.05 vs 0.07±0.02mm², P＜0.01). Intima and media area were no significant difference between B group and C group. Lumen area in A group were significantly decreased, compared with in B group and C group (0.06±0.04 vs 0.35±0.16mm²; 0.06±0.04 vs 0.20±0.15mm², P＜0.01). Lumen area in A group were significantly increased compared with in C group(0.35± 0.16mm² vs 0.20±0.15mm², P<0.05)3. The C group and the A group were significantly decreased, compared with the CRP concentration on post-operative, 1 day (7.83±1.17 vs 13.81±4.30μg/mL, P＜0.01), 7days (5.67±0.41 vs 9.38±2.99μg/mL, P<0.01), 14 days (5.58±0.67 vs 6.88±0.92μg/mL, P<0.05), respectively. There were no significant difference between B group and C group.4. The A group and the B group were significantly increased, compared with the CNP concentration on post-operation, 1 day (16.38±3.76 vs 4.20±0.84μg/mL, P<0.01), 7 days (10.81±3.37 vs 4.58±2.18μg/L, P<0.01), 14 days (6.94±2.73 vs 4.33±0.98μg/L, P<0.05), respectively. CNP returned to pre-operation level at 28 days after balloon injury.Conclusions:1. Experimental animal model of stenosis can be set up successfully.2. CNP might influence the process of femoral artery recovery after balloon injury in diabetic rabbit.3. Exogenous CNP maybe suppressed the femoral artery inflammation in diabetic rabbits, it maybe suppressed the femoral artery angiostenosis in diabetic rabbits.