Preventive Effect Of Soluble Guanglate Cyclase Activator Cinaciguat In Diabetes Macrovasculopathy

Backgrounds:According to the international diabetes federation, the world has reached 285 million, patients with diabetes, expected to rise to 500 million by 2030, more than three-quarters of the patients died of cardiovascular complications, cinaciguat, a new type of soluble guanglate cyclase (sGC) activator, its research in the therapeutic areas of cardiovascular disease and other diseases have been explored. Especially in the aspects of the therapeutic of cardiovascular diseases.cinaciguat have become the focus in the medical community, but its specific mechanism in the therapeutic of cardiovascular diseases and the scope of the therapeutic is not fully clear. The proportion of diabetic patients complicated with cardiovascular disease as much as the rest of the population. Macrovasculax complications are the leading causes of increased morbidity and mortality in diabetic patients. Therefore,it is very important to explore cinaciguat weather have the function of preventive in diabetes macrovasculopathy.Objective:Obejective to analyze the effect of soluble guanglate cyclase activator cinaciguat on oxidative stress, blood fat and adhesion molecule of the type 2 diabetes rats. Evaluating its protection in diabetes macrovasculopathy, and discussing its mechanism.Methods:1. Type 2 Diabetes was induced by feeding with high lipid and glucose diet and Streptozotocin(STZ) injection (30 mg/kg) intraperitoneally (i.p).2.The rats were divided into five groups:control, diabetic, diabetic-cinaciguat low dose [3.5ug/(kgd)], diabetic-cinaciguat moderate dose [7ug/(kg·d)] diabetic-cinaciguat high dose [14ug/(kg·d)]3.After fet 12 weeks and treatment for 2 weeks, testing lipid contents of various groupsby full automatic biochemical analyzer.For total superoxide dismutase (T-SOD) activity and malonaldehyde (MDA) content by colorimetry, and for endothelin 1(ET-1) content by ELISA.4.Histopathological examinations was performed using hematoxylin and eosin (HE) stain.5.Meanwhile, the expression of intercellular adhesion molecule 1 (ICAM-1) and vescular cell adhesion molecule 1(VCAM-1) were detected by immunohistochemistry and Real-time PCR.Results:l.Our data showed that the diabetic groups treated with cinaciguat at low, moderate and high doses had significantly lower levels of the triglyceride (TG), total cholesterol(TC) malonaldehyde(MDA) and endothelin-1(ET-1) concentrations and higher levels of total superoxide dismutase(T-SOD) activity than did the diabetic control group at the end of the study (each P<0.05).2.cinaciguat not decreased the blood glucose levels and weight significantly in the diabetic rats (P＜0.05).3.Hematoxylin and eosin (HE) staning demonstrated the irregularities in the arrangement of elastin fibers in model group.With cinaciguat-treat, improvement was seen in the arramgement of aortic media and macrovasculopathy was obviously alleviated.4.Compare with DM Group, cinaciguat-treated groups showed significant increase in the expression of ICAM-1 and VCAM-1 were detected by immunohistochemistry and Real-time PCR(each P>0.05).Conclusion:1.cinaciguat might regulate the blood lipid content, decrease the oxidative stress level and improved the function of vascular endothelial cells.2.Through pathological section, cinaciguat can be observed in vascular endothelial cells and smooth muscle change have certain improvement effect, thus improving diabetes early vascular smooth muscle proliferation.3.cinaciguat may be reduce the expression of ICAM-1 and VCAM-1, playing an important role in the prevention and treatment of diabetic macroangiopathy.