| Objective:To research the changes of ET-1, IL-6level pre and pro the fat-loading, on the relationship with atherosclerosis.Methods:Selected20healthy Male New Zealand white rabbit (2to3months of age,2.5-3kg),were randomly divided into non-intervention group and drug intervention group(n=10). All experimental animals were fed with high cholesterol diet (containing1%cholesterol,) for12weeks.The drug intervention group were given additional fenofibrate (25mg/Kg/d). all experimental animals were given a high-fat meal load (containing2%cholesterol,8%egg yolks,90%basic feed), On the initial,4th,8th and12th week successively, taken the blood at fasting,and2nd,4th,6th,8th hour and measured plasma endothelin1(ET-1), interleukin-6(IL-6) concentrations. During the same period, ultrasound image were taken to observe changes of abdominal aorta wall (ultrasound scores); All rabbits were killed at the end of the experiment. Abdominal aorta hardening were observe with HE staining.Results:1. In the process of hardening of the arteries, Changes of plasma ET-1pre and pro the fat-loading:1.1non-intervention groupThe level of ET-1had been gradually increasing in the process of the experiment (at the fasting, P<0.05; pro the meal, P>0.05), and the level of ET-1was the highest at each experiment time point pre and pro the meal on the4th week(P>0.05). In addition, at the beginning of experiment, It was the highest at the4th hour pro the meal (P<0.05); the highest level appeared at the2" hour pro the meal on the4th,8th,12th week,(the level of ET-1on the4th,8th week, P>0.05; the level of ET-1on the12th week, P<0.05).1.2Drug-intervened groupDuring the experiment, the level of ET-1was the higest on the4th week(at fasting, P<0.05; pro the fat-loading, P>0.05). After the4th week, the level of ET-1 decreased firstly and increased subsequent at fasting and the8th hour pro the meal(higher than the initial, P>0.05), and were lower than the initial at the2nd,4th,6th,8th hour (P>0.05). In addition,on the initial the level of ET-1were elevated at each time point pro the meal (the most significant at the4th hour, P<0.05) It’s rising time extended as the experiment progress,(the higest at the6th hour on the4th,8th week, P<0.05; still lower at the8th hour than that of at fasting on the12th week, P>0.05).2. In the process of hardening of the arteries, changes of IL-6pre and pro the fat-loading2.1Non-intervention groupDuring the experiment, the level of I1-6was the highest at the fasting and each time point pro the meal on the4th week(P>0.05), their levels decreased after the4th week (belower than the initial, P>0.05); And compared with fasting It’s level was the highest on the initial and4th hour (P>0.05), It was a little high at the4th to8th hour on the4th week(the higest6th hour, P>0.05), and decreased at the2-6th hour after the meal on the8th week (the lowest at the41h hour, P<0.05), and was slightly higher at the8th hour (P>0.05), and were low at each time piont after the meal on the12th week1(the minimum at the4th hour,P<0.05).2.2Drug-intervened groupDuring the experiment, the level of IL-6gradually increased at fasting (P>0.05), It firstly rise and then reduced at the2th hour pro the meal(the highest on4th week, P>0.05). It were low at4th hour after the meal(the minimum on the8th week,P>0.05), and the values of IL-6show a sine wave fluctuations at6-8h pro the meal(low, On the initial,8th and12th week).It’s level had a little more than fasting at each time point after the meal on the initial,4th week (the higest at the6th hour),and went down firstly, then up at the2nd,4th hour on the8th week (the higest at the6th hour, P>0.05).0.05).It was the the highest at fasting on the12th week,however, It slightly decreased at each time point pro the meal (P>0.05).3. Arteries by ultrasound test3.1Ultrasonoscopy With the process of experiment,animals’aortaventralis appeared the following changes in two groups:If’s IMT aortaventralis grew thick gradually and inner membrane became rough. At the end of the experiment (12weeks), plaque could be observed.3.2Ultrasound scores of aortaventralis in different groups F=322.667,P<0.05;It shows significant interactions:F=7.692,P=0.007.4. In the process of hardening of the arteries, the relationship of ET-1with AS (ultrasound scores) pre and pro the fat-loading.4.1Non-intervention group(1) On the4th week,there was a reverse correlation at the6th hour pro the fat-loading, the rest was positively correlation (at the8th hour best),P>0.05(2) On the8th week, there was a positive correlation at the2th and4th hour (best, at the2nd hour), the rest was a reverse correlation(best,at the6th hour), P>0.05(3) On the12th week, there was a positive correlation at the6th,8th hour (P>0.05,best at the8th),the rest was a reverse correlation(especially at the2nd hour, P<O.O5;at the4th hour, P>0.05)4.2Drug-intervened group(1) On the4th week, there was a reverse correlation at the8th hour, and a positive correlation at the rest of the time point(especially at the2nd hour), P>0.05(2) On the8th week, there was a reverse correlation at the4th and6th hour, and a positive correlation at the rest of the time point(especially at the fasting time), P>0.05(3) On the12th week, there was a reverse correlation at the4th and6th hour(especially at the4th hour), and a positive correlation at the rest of the time point(especially at the fasting time) P>0.055. In the process of hardening of the arteries, the relationship of IL-6with AS (ultrasound scores)pre and pro the fat-loading5.1Non-intervention group(1) On the4th week, there was a positive correlation at the fasting and2nd hour(especially at the2n hour, P<0.05), and a reverse correlation at the rest of the time point(especially at the8th hour,P<0.05; at the4th,6th hour, P>0.05) (2) On the8th week, there was a positive correlation at the4th and6th hour (especially at the6th hour), and a reverse correlation at the rest of the time point(especially at the8th hour) P>0.05(3)On the12th week, there was a positive correlation at the8th hour, and a reverse correlation at the rest of the time point(especially at the the fasting time), P>0.055.2Drug-intervened group(1) On the4th week, there was a reverse correlation at the2nd,6th and8th hour(especially at the8th hour), and a positive correlation at the rest of the time point(especially at the4th hour), P>0.05(2) On the8th week, there was a positive correlation at the each time point pro the lly at the2nd hour), P>0.05(3) On the12th week, there was a positive correlation at the6th hour (P>0.05), and a reverse correlation at the rest of the time point(especially at the2nd hour,P<0.05)6. Animal abdominal aortic pathological observation:Normal artery:endothelium is integrated, without "empty plasma phenomenon" and foam cells; Non-intervention group (in the12th week):there is some damage to the endothelium with endothelial cells and smooth muscle cell proliferation significantly. The vascular wall is looser than normal artery, along with "empty plasma phenomenon" and foam cells; drug-intervened group(in the12th week):endothelium is integrated, and there are slightly hyperplasia of smooth muscle cells and a small amount of foam cells, accidentally the phenomenon of" empty plasma phenomenon ".Conclusion:1. The average level of plasma ET-1reveals a tendency of increasing during the process of AS pre and pro the fat-loading. It indicates fat-loading could influence the level of plasma ET-1,and it maybe increase the risk of endothelial injury in AS.2. At the beginning of AS, inflammatory reaction in endothelial is quite severe. However, with the process of AS, the inflammatory reaction is alleviated gradually. What’s more, fat-loading could ease this process further, the mechanism of which still need further investigation.3. Taking The blood sample4-6hours after fat-loading could reveal the relative situation of AS more accurately. |
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