白藜芦醇对兔动脉粥样硬化血脂及反映斑块稳定性的MMP-9/TIMP-1比值的影响

Effects of resveratrol on lipid profile and MMP-9/TIMP-1 ratio reflected plaque stability in rabbits with atherosclerosis

目的:观察白藜芦醇对动脉粥样硬化兔血脂代谢、主动脉过氧化物酶体增殖物活化受体γ(PPARγ)、基质金属蛋白酶-9(MMP-9)、组织基质金属蛋白酶抑制因子-1(TIMP-1)表达的影响。方法:将70只雄性新西兰白兔随机分为5组:A组喂普通饲料,B组喂高脂饲料,C、D、E组喂高脂饲料的同时分别给予白藜芦醇4mg/kg.d、8mg/kg.d、16mg/kg.d进行干预。于12周末取血测定血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)和高密度脂蛋白-胆固醇(HDL-C)水平,酶联免疫吸附试验(ELISA)法测定血清MMP-9、TIMP-1水平。取完整胸主动脉,逆转录聚合酶链反应(RT-PCR)观察主动脉PPARγ、MMP-9、TIMP-1mRNA的表达。结果:病理对照组(B组)TG[(2.46±0.32)mmol/L∶(0.42±0.23)mmol/L]、TC[(30.19±3.98)mmol/L∶(1.07±0.22)mmol/L]、HDL-C[(1.74±0.50)mmol/L∶(0.63±0.30)mmol/L]、LDL-C[(16.82±1.95)mmol/L∶(0.53±0.15)mmol/L]、PPARγ[(0.78±0.07)∶(0.59±0.05)]、TIMP-1[(91.80±9.23)ng/ml∶(68.49±9.04)ng/ml]、MMP-9[(341.96±9.94)ng/ml∶(164.04±7.08)ng/ml]水平均明显高于正常对照组(A组)(P均<0.01);随着白藜芦醇剂量的增大,血清TG、TC、LDL-C水平,MMP-9及其mRNA表达,和MMP-9/TIMP-1比值显著降低,HDL-C、TIMP-1及其mRNA表达显著升高,在中、高剂量组(D、E组)更为明显(P<0.05～0.01),呈一定的剂量依赖性。结论:白藜芦醇可改善兔动脉粥样硬化血脂代谢紊乱,通过降低MMP-9/TIMP-1比值稳定粥样硬化斑块。

Objective： To investigate the effects of resveratrol on lipid profile and the mRNA expressions of peroxisome proliferators--activated receptory （PPAR-- 7）, matrix metalloproteinase-- 9 （MMP-9） and tissue-- inhibitor of metalloproteinase-1 （TIMP- 1） on aorta in rabbits with atheroselerosis. Methods： Seventy male New Zealand white rabbits were randomly divided into five groups： group A （normal control group）, group B （pathological control group）, group C （treated with low dosage resveratrol4 mg/kg· d）, group D （treated with mid dosage resveratrol 8 mg/kg· d）, and group E （treated with high dosageresveratrol 16 mg/kg· d））. At the end of 12 th week, serumtri- glyceride （TG）, total cholesterol （TC）, low density lipoprotein-cholestcrol （LDL-C） and high density lipoprotein-cho- lestero/ （HDL-C） in the rabbits were detected by biochemical method. The mRNA expressions of PPAR - γ, MMP-- 9 and T1MP-1 on aortae were examined by semiquantitative reverse transcription polymerase chain reaction （RT-- PCR）. Serum MMP--9 and T1MP--1 levels were measured by enzyme-linked immunosorbent assay （ELISA）. Re- suits; For pathological control group （group B）, the levels of TG[（2.46±0.32）mmol/L：（O.42±0.23）mmol/L]、TC[（30.19±3.98）mmol/L：（1.07±0.22）mmol/L]、HDL-C[（1.74±0.50）mmol/L：（0.63±0.30）mmol/L]、LDL-C[（16.82±1.95）mmol/L：（0.53±0.15）mmoll/L]、PPAR7[（0.78±0.07）：（0.59±0.05）]、TIMP1[（91.80±9.23）ng/ml：（68.49±9.04）ng/ml]、MMP-9[（341.96±9.94）ng/ml：（164.04±7.08）ng/ml] were significantly higher than those of normal control group （group A） （P〈0.01 all）. As the dosage of resveratrol increased, the levels of serum TG, TC, LDL-C, MMP--9 and expressions of their mRNA, MMP-9/TIMP-1 ratio decreased, and the levels of serum HDL-C, TIMP 1 and expressions of their mRNA in- creased. It＇s specially obvious in mid and high dosage groups （group D and E） （P〈0.05-0.01） with dose-dependent. Conclusion： Resveratrol can improve dyslipidemia in rabbits with atherosclerosis. It might strengthen the plaque stability through regulating the MMP 9/TIMP-1 ratio.