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Objective To investigate the effect of DPP-4 inhibitor sitagliptin on atherosclerosis and its mechanism.Methods Thirty male ApoE-/-mice were randomly divided into two groups:experimental group(n=15) and control group(n=15).The mice in the experimental group were fed with high-fat mixture of sitagliptin and the control group was fed with high fat.Collected blood in the eyeballs in order to analyze serum levels of blood lipids and blood glucose after 16 weeks of feeding,and detected serum nitric oxide synthase(eNOS),vascular adhesion molecule-1(VCAM-1) with ELISA method.Collected aortic tissue in order to analyze atherosclerotic plaque.Results There was no significant difference in blood glucose,triglyceride and total cholesterol level between the two groups(P>0.05).The serum high density lipoprotein in the experimental group was significantly higher than that in the control group(P<0.05).The atherosclerotic plaque in the experimental group(7.55±1.87)%, which was significantly smaller than that in the control group(11.67±1.32)%.The serum VCAM-1 in the experimental group was lower and the eNOS was higher than that in the control group(P<0.05).Conclusion DPP-4 sitagliptin can increase the expression of HDL and eNOS and inhibit the expression of VCAM-1,thereby inhibiting the progression of atherosclerosis in ApoE-/-mice.
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Objective To investigate the expression of apelin and its recoptor (APJ) in myocardium in insulin-resistant CIR rats with myocardial ischemia.Methods Totally 24 male SD rats were randomly divided into three groups:IR group,IR+ischemia group,the control group (n=8 each).Rats in IR and IR+ischemia groups were fed with the high fat diet.Rats in control group were given the basic diet.The rat model of insulin resistance was assessed by fasting blood glucose (FBG),fasting insulin (Fins) and insulin resistance index (HOMA-IR).The rat model of myocardial ischemia was conducted by subcutaneous injection of isoprenaline 1 mg/kg per day in IR+ ischemia group.The other groups were injected an equal volume of saline.The expression levels of apelin and APJ mRNA in myocardium were determined by real-time-PCR.The positive expression of apelin polypeptide was detected by immunochemistry.Results Compared with the control group,the apelin average optical density was increased in IR group and was decreased in IR+ ischemia group [(0.16±0.004) vs.(0.13±0.005),(0.10±0.002) vs.(0.13±0.0050),both P＜0.05].There was a significant difference in apelin average optical density between IR group and IR+ischemia group [(0.16± 0.004) vs.(0.10±0.002),P＜0.05].Compared with the control group,the relative expression of apelin mRNA was increased in IR group [(5.89±0.36) vs.(4.40±0.24),P＜0.05]The relative expression of apelin mRNA was decreased in IR± ischemia group as compared with IR group [(2.66 ± 0.17) vs.(5.89 ± 0.36),P ＜ 0.05].The APJ mRNA relative expression was increased in IR group as compared with control group and was decreased in IR+ ischemia group as compared with IR group [(10.46±1.06) vs.(6.54±0.63),(3.31±0.31) vs.(10.46±1.06),both P＜0.05].Conclusions The expressions of apelin and APJ are inhibited in insulin-resistant rats with myocardial ischemia,which attenuates their protective effects on myocardium.
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Objective To evaluate the angiogenic effect of the bone marrow mesenchymal stem cells (MSCs) transfected with adeno-associated virus (rAAV) -mediated human vascular endothelial growth factor 165 (VEGF165) gene, to detect the expression and bioactivity of VEGF in the MSCs.and to detect the expression and bioactivity of VEGF165 gene in the area of ischemic skeletal muscle in rats. Methods The MSCs were cultured by whole bone marrow culture method, then the MSCs were transfected with rAAV-VEGF165, the expression of VEGF was examined using ELISA and RT-PCR. The model of ischemic skeletal muscle was established by ligation in inbred rats. The rats were injected with PBS at the ischemic zone (group A), MSC (group B), hVEGF-transfected MSC (group D), and 7 days later they were injected with hVEGF transfected MSC (group C). Six weeks after the transfection, the capillary density of the ischemic zone was examined by factor Ⅷ stain. Results The MSCs were cultured successfully according to the expressions of positive CD44 and CD90,negative CD34. In rAVV-VEGF165 transfected group, the secretion levels of VEGF165 in supernatant were significantly higher than in non-transfected group 1,3,5,7 and 9 days after injection [(131. 98±6.00) ng/L vs. (68. 72±1.99) ng/L; (263. 96±4.58) ng/L vs. (76. 47±4.98) ng/L;(540. 85±5.97) ng/L vs. (89. 86± 1.99) ng/L; (208. 98± 5.06) ng/L vs. (84. 93±8. 97) ng/L;(174.45±5.00) ng/L vs. (68.71±5.98) ng/L, all P＜0.05]. On the position of 579 bp, highbrightness strip could be seen. There were no significant differences in growth curve and cell morphology between transfected group and non-transfected group. Six weeks after the transplantation, the capillary density was significantly greater in group D [(9.35 ± 2.72)/ vision]than in group A [(1. 05±0. 50)/vision] ,group B [(3.10± 1.43)/vision, both P＜0. 01)] and group C [(6. 95± 1.69)/ vision, P＜0. 05] Conclusions MSCs are helpful for the stable expression of hVEGF gene, and it is good cellular vehicle for VEGF genes. The effect of combined therapy is much better than separate transplantation of MSCs. The best time to transplant is 10 days after surgical operation.
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Objective To assess the values of TIMI myocardial perfusion grade (TMP), corrected TIMI frame count (CTFC), sum-ST-segment resolution (sumSTR), max-ST-segment deviation (maxSTE) in judging myocardial perfusion and to predict their clinical outcomes. Methods In 77 patients with AMI, methods of TMP, maxSTE, sumSTR, CTFC were used to judge myocardial perfusion grade respectively immediately after PCI. Sixty-five patients underwent 99m Tc-MIBI/ 18 FDG DISA SPECT within one months after PCI, in-hospital heart faiures and cardiac events in the 6 months were recorded. Results Compared with 99m Tc-MIBI/ 18 FDG DISA SPECT, sensitivity, specificity, accuracy of TMP, CTFC, maxSTE, sumSTR was calculated. Sensitivity, specificity, accuracy of maxSTE were 80%, 85.7%, 83.1% respectively; Those of TMP were 73.3%, 80%, 76.9%, respectively. But those of CTFC (40), CTFC (30), sumSTR (30%), sumSTR (50%) were lower. By multivariate analysis of TMP0/1, maxSTE was the independent risk factor for 6-month cardiac events. Conclusion TMP, maxSTE may better assess myocardial perfusion, and accurately predict the outcome in 6-months.