Effects Of Simvastatin On The Expression Of VEGF, TGF-β1 And CTRP3 In Type Ⅱ Diabetic Rats With Atherosclerosis

Object: To investigate the expression of vascular endothelial growth factor(VEGF), transforming growth factor-β1(TGF-β1) and C1q/tumor necrosis factor-related protein 3(CTRP3) in type II diabetic rats with atherosclerosis and the interventional effection mechanism of simvastatin on type II diabetic rats with atherosclerosis.Methods:(1) 3-weeks-old male rats(weight 160g~200g) after daptive feeding one week were randomized into normal control(NC) group(n = 8), high-fat diet(HFD) group(n = 8), high-fat diet intervention(HFD+S) group(n = 8), model group(M group that diabetic arteriosclerosis group, n = 28) and model intervention group(M+S group that diabetic arteriosclerosis after intervention, n=16).(2) Using a master single intraperitoneal injection of streptozotocin with 45 mg/kg, vitamin D3 fractionation intragastric administration by a total dose 500000 U/kg and high-fat diet feeding to establish the type II diabetic rats with atherosclerosis model. The blood glucose levels and thoracic aorta common histomorphology inspection were used to evaluate animal model success.(3) The group HFD+S and group M+S rats were perfused with simvastatin at 20 mg/(kg·d) as intervention. The group NC, group HFD and group M rats were given distilled water [20 m L/(kg·d)] instead.(4) The contents of fasting plasma glucose(FPG) were detected by dry chemical method. The levels of fasting insulin(FINS) were detected by radio-immunity.The levels of TC, TG, LDL and HDL were detected by whole automatic biochemical detection. The contents of VEGF, TGF-β1 and CTRP3 were measured by enzyme-linked immunosorbent assay(ELISA).Results:(1) histomorphology: The group NC and group HFD+S had no pathological changes under light microscope. The group HFD showed a little foam cells in artery. Characteristics of atheromatous plaque were found in group M. The plaque’s surface had a fibrous cap that varying amounts of foam cells could be seen, which deeply contained large amounts of necrotic materials, lipid depositions, cholesterol crystals and calcium depositions. Medial smooth muscle fibers were hyperplasia and irregular, elastic fiber fracture. The changes of pathology were markedly attenuated in group M+S.(2) The levels of FINS, HOMA-IR, VEGF,TGF-β1 and CTRP3 were significantly higher in group HFD than those of group NC. The levels of body weight and FINS were significantly lower in group M than those of group NC. The levels of FPG,HOMA-IR, TC, TG, LDL, VEGF and TGF-β1 were significantly higher in group M than those of group NC. The levels of TGF-β1 and CTRP3 were significantly higher in group HFD+S than those of group HFD.The levels of body weight, FINS and CTRP3 were significantly lower in group M than those of group HFD.The levels of FPG, TC, TG, LDL, HDL and VEGF were significantly higher in group M than those of group HFD. The levels of FPG, TC, TG, LDL, HDL and VEGF were significantly lower in group M+S than those of group M. The level of FINS, TGF-β1 and CTRP3 were significantly higher in group M+S than those of group M(P<0.05).(3) In correlation analysis, VEGF showed a negative correlation with body weight and FINS, and had a positive correlation with TC, TG, LDL, FPG and HOMA-IR. TGF-β1had a positive correlation with CTRP3 and TG, and showed a negative correlation with HDL. CTRP3 had a positive correlation with TGF-β1, and showed a negative correlation with TC and HDL.(4) In a stepwise multiple regression analysis, FPG, TG, HDL and LDL were independent risk factors for plasma VEGF level. CTRP3 was independent risk factor for plasma TGF-β1 level. TG and TGF-β1 were independent risk factors for plasma CTRP3 level.Conclusion:(1) VEGF, TGF-β1 and CTRP3 may participate in the occurrence of diabetic atherosclerosis.VEGF can promote the occurrence of diabetic atherosclerosis. TGF-β1 and CTRP3 may have a protective effect on diabetic atherosclerosis.(2) Simvastatin can regulate the levels of blood lipids, improve islet fuction, decrease glucose, down regulate serum level of VEGF and up regulate serum levels of TGF-β1 and CTRP3 to attenuate the diabetic vascular disease. Whether simvastain in humans also has the same result was to be futher studied.