| The expression of LOX-1 in vasculopathy of type 2 diabetesmellitus rats and the effects of probucolObjective:LOX-1 is a main receptor of oxidized LDL on vascular endothelialcell, it induces the endothelial dysfunction and iujury by increasingoxidized LDL. The main purpose of this study:(1)To investigate the simple,economical and efficient way of establishing type 2 diabetesmellitus(T2DM) rat model. (2) To observe the expression of LOX-1 invasculopathy of macrovascular of T2DM rat model in the initial stage andthe influencing factors. (3) To analyse the effect of probucol for theexpression of LOX-1 in vasculopathy of macrovascular of T2DM rat modeland the mechanism of the effect.Methods: 50 Healthy SD male rats, divided into four groups randomly:GroupA(the diets enriched with fat and suger 8 weeks plus low dose STZ inducedT2DM rat model successfully and then probucol 500mg/kg/d intervence for8 weeks);Goup B(At first the diets enriched with fat and suger and probucol500mg/kg/d intervence for 8 weeks then low dose STZ induced T2DM rat modelwith probucol 500mg/kg/d intervence 8 weeks);Group C(the diets enrichedwith fat and suger 8 weeks and than low dose STZ induced T2DM rat model8 weeks);Group D(normal control group).After divided into groups, the ratsof group A, B and Cwere given the high-glucose-high-fat diets. After sixweeks, the rats were given intragastric administration with fat milk1ml/100mg weight. At the eighth weekend, the level of plasma insulin wasdetected, the results showed that the level of plasma insulin in thehigh-glucose-high-fat diet group was significant higher than normalcontrol group. On the next day morning, the weight of the rats were measured and the vena caudalis of the rats were injected with STZ(30mg/kgweight);three days later the weight of the rats were measured'again, thevena caudalis of the rats were injected with STZ(30mg/kg weight) again.One week after the second injection, we tested the blood glucose of therats, if the result of the blood glucose was higher than 16.7mmol/l, it wassucceed to establishing the T2DM rat model. After establishing the T2DMmodel, the rats were given the high-glucose-high-fat diet until 8 weekslater, and then killed. The serum insulin and lipid of the rats weretested. The ROS of the aorta of the rats in frozen section were tested, theexpression of LOX-1 in the aorta of the rats were tested by RT-PCR andWestern blot. All data were analyzed using the SPSS 13.0 PC program forwindows.Results: After 8 weeks of the diets enriched with fat and suger, the seruminsulin of group A, B and C were significant higher than groupD(P=0.000), the achievement ratio of STZ induced T2DM model were 91.67%. Atthe end of the experiment, the serum TG, TC and LDL-C of group A,B andC were significant higner than group D (P=0.000; P=0.000; P=0.000;P=0.000), the serum TC and LDL-C of group A and B were significant lowerthan group C (P＜0.05; P＜0.05), the serum TC and LDL-C had no significantdifference between group A and B (P＞0.05).The aorta of group. C rats hademerged initial macro-vasculopathy. There were almost no lesions in groupA and C. The ROS results of the aorta of every group showed thatfluorescence intensity of group C were highest, group A and B werelower, group D were the lowest. Comparing with group D, the expression ofmRNA level and protein level of LOX-1 in the arota of group A, B and Cwere significant higher (P=0.000; P=0.000). The expression of mRNA leveland protein level of LOX-1 in the arota of group A and B were significantlower than group C(P＜0.05;P＜0.05),The expression of mRNA level and protein level of LOX-1 in the arota of group A and B had no significant difference(P＞0.05).Conclusions: (1) Usingthehigh-glucose-high-fat diet plus low dose STZ,the T2DM rat model can be induced successfully and simplely. (2)Theexpression of LOX-1 can increase in the initial macro-vasculopathy of T2DMrats. (3)Probucol can decrease the expression of the LOX-1 in the bloodvessel of T2DM rat model, the mechanism refer to the decreased levels ofTC and LDL-C and ROS. (4) Probucol can influence the macro-vasculopathyof DM by decreasing the expresson of the LOX-1 in vascular endothelialcells. |
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