【作者】 管庆林；

【导师】 朱继金；

【作者基本信息】 广西医科大学 ， 心血管内科学， 2010， 硕士

【摘要】 目的探讨大鼠经高钠盐与高脂肪复合喂养后血压、血脂、主动脉构型变化和中层粥样硬化改变以及辛伐他汀的阻断作用方法随机选取60只成年雄性SD大鼠,随机分为5组,分别为正常对照组(N组)、高脂摄入组(F组)、高盐摄入组(S组)、高盐高脂复合摄入组(SF组)、高盐高脂加辛伐他汀组(T)组,分别予以标准饲料(0.4%食盐与0.2%胆固醇)、高脂饲料(1.2%胆固醇,0.4%食盐)、高盐饲料(4.4%食盐、0.2%胆固醇)、高盐高脂复合饲料(4.4%食盐、1.2%胆固醇)及高盐高脂复合饲料加辛伐他汀(0.2mg／kg)喂养10周后,测量各组大鼠体重、鼠尾血压计测量动脉压、心率,处死动物后测定血清甘油三酯与总胆固醇的浓度；取主动脉环起始段,以10μm间隔厚度行冰冻切片进行油红0和苏木精染色观察动脉中层粥样硬化情况；常规苏木精-伊红染色计算动脉中膜层厚度与动脉内腔面积与血管腔总的面积比值。结果(1)FS组、F组、S组的收缩压分别为170.5±14.787 mmHg、148.95±27.383mmHg、156.4±18.010mmHg,舒张压为131.315±9.00mmHg、116.7±5.147mmHg、131.589±11.548 mmHg,与N组相比,上述三组血压明显增高(P<0.001),而T组与N组比较也增高(P<0.001),但较FS组明显降低,(P<0.05)。FS组心率(438.70±20.166次／分)与其他组比较明显增高(P<0.001),而F组与S组(411.4±19.132次／分、409.00±10.424次／分)与N组和T组比较,无显著差异；同样,N组比,FS组与F组体重明显高于N组(412.34±45.61g,390.86±35.55g,P<0.001),而T组体重则明显低于N组(344.48±27.59g,P<0.001),S组、FS组与F组之间未见明显差异。(2)F组与FS组血脂总胆固醇明显增高(1.875±0.133 mmol／L、2.036±0.177 mmol／L),同时该两组甘油三酯也明显增高(1.062±0.070 mmol／L、1.256±0.085 mmol／L),与N组和T组比较明显升高(P<0.001),而S组与N组无明显差异。(3)S组、F组与FS组大鼠动脉构型也明显异常,动脉中膜厚度为(135.28±12.29μm、158.86±15.23μm、184.00±13.40μm),与正常组比较明显增厚(P<0.001)；同时大鼠动脉内腔面积与血管腔总的面积比值也存在明显异常,FS组、F组动脉内腔面积／血管腔总面积比值明显减少(分别为66.7±6.91,72.9±4.90)与正常组比较明显变小(P＜0.05)。(4)病理切片H-E染色中FS组均表现为中膜增厚,其中50%大鼠出现典型的动脉粥样硬化改变,油红0染色提示血管壁出现明显脂肪浸润；而同时F组大鼠亦表现为中膜增厚,但程度较FS组轻,仅30%出现粥样硬化斑块,油红0染色提示脂肪浸润；而S组与辛伐他汀治疗组无动脉粥样硬化改变,仅表现为中膜增厚。结论1.通过高盐高脂复合刺激后,大鼠的血压明显升高,而复合刺激改变明显强于单一因素,表明通过高盐高脂喂养可以建立类似代谢异常所致的而高血压大鼠模型；2.高盐高脂复合喂养的大鼠动脉发生动脉内膜呈内向型增厚和粥样硬化,可以制备代谢因素异常所致动脉粥样硬化模型,同样复合刺激改变明显强于单一因素；3.他汀类药物对大鼠动脉血管重构和粥样硬化过程具备明显阻断作用。更多还原

【Abstract】 Objective To study the changes of blood pressure,blood lipids,conformational changes and aortic atherosclerosis in rats after combined high salt and rich fat diet ingestion as well as the possible blocking role of simvastatin in process.Method a total of 60 adult male SD rats were randomly divided into 5 grous, namely normal control group (N group),rich fat intake group (F group) and high salt intake group (S group), high salt with rich fat intake group (SF group),rich fat with high salt plus simvastatin group (T group) and were given standard diet (0.4%,0.2% salt and cholesterol), high fat diet (1.2% cholesterol,0.4% salt) high salt diet (4.4% salt,0.2% cholesterol), high salt compound fat diet (4.4% salt,1.2% cholesterol) and high salt with rich fat diet plus t simvastatin (0.2mg/kg) after 10 weeks measured weight,measured blood pressure, heart rate using tail-cuff sphygmomanometer of rats in each group, was collected to determine serum concentrations of triglyceride and total cholesterol; get ascending aortic root initial segment of aortic rings to 10μm thickness intervals do Frozen sections were oil red O and hematoxylin staining of the middle artery atherosclerosis situation; routine hematoxylin-eosin staining in the calculation of film thickness and arterial arterial lumen area and lumen area ratio of the total.Results (1) FS group, F group, S group were systolic blood pressure (170.5±14.787 mmHg、148.95±27.383mmHg、160.4±18.010mmHg), diastolic blood pressure (131.315±9.00mmHg、116.7±5.147mmHg、131.589±11.548mmHg) compared with N group, the three blood pressure was significantly higher (P <0.001), while the T group compared with N group also increased, but significantly lower than the FS group, (P<0.05). FS group heart rate (38.70±20.166 beats/min) compared with the other group differences (P<0.001), while the F group and S group (411.4±19.132 beats/min,409.00±10.424beats/min) and the N group and the T group, no difference; Similarly, N group than, FS group and F group body weight was significantly higher than N group (412.34±45.61g,390.86±35.55g, P<0.001), whereas body weight was lower than T N group (344.48±27.59g, P<0.001), S group, FS group and no significant difference between the F group.(2) F group and the FS fat group was significantly higher total cholesterol and blood lipid (1.875±0.133mmol/L,2.036±0.177mmol/L), while triglyceride was also significantly increased in the two groups (1.062, with the N group and T group was significantly higher (P<0.001), while the S group and N group no significant difference.(3) S group, F group and the FS group was significantly abnormal arterial configuration, arterial medial thickness(135.28±12.29μm,158.86±15.23μm, 184.00±13.40μm),thickened with the normal group (P<0.001); while arterial lumen area and lumen area ratio of the total there are obvious exceptions, FS group, F Group artery lumen area/total area ratio was significantly decreased (66.7±6.91,72.9±4.90) compared with the N group was significantly smaller (P<0.05).(4) HE staining of biopsy 50% FS group in rats the typical atherosclerotic changes in the membrane showed thickening of the remaining oil red O staining showed significant fatty infiltration of the vessel wall; while at the same group of 30% F atherosclerotic plaques occurs, oil red O staining showed fatty infiltration; the S group and simvastatin group without atherosclerotic changes, manifested in the film thickness.Conclusion 1. The rat’s blood pressure rise significantly after high salt or fat ingestion, which is enhanced by combined two factors, indicating the hypertensive rat model can be established by high salt with rich fat diet2. Diet combined high salt and rich fat can induce arterial intima thickening and atherosclerosis,the pathologic process can be blocked by Statins, which simulate the clinic situation.更多还原