缬沙坦对动脉粥样硬化大鼠模型主动脉内皮细胞保护作用及对血浆内皮脂肪酶水平影响

Effects of valsartan on aortic endothelial cells and plasma endothelial lipase levels of atherosclerosis rat model

目的:通过血管紧张素Ⅱ受体阻断剂(angiotensinⅡreceptor blocker,ARB)对动脉粥样硬化性大鼠模型进行治疗,探讨ARB对主动脉内皮细胞保护作用。方法:30只Wistar大鼠随机分为3组,每组10只,模型组通过高脂饲料建立动脉粥样硬化大鼠模型,实验组增加缬沙坦干预,8周后比较各组主动脉内皮一氧化氮(nitric oxide,NO)、内皮素(endothelin,ET)、细胞色素c(cytochrome,Cyt-c)及内皮脂肪酶(endothelia lipase,EL)水平。结果:实验结束时,模型组HE染色可见明显斑块形成并伴有大量脂质细胞浸润,Cyc-c免疫组化染色显示内皮细胞凋亡阳性率(36.85±12.45),高于对照组(0.81±0.11)和实验组(13.85±6.41)(P=0.000),平滑肌细胞凋亡阳性率(9.65±2.62)高于对照组(0.06±0.01)(P=0.000),但与实验组(7.85±1.34)差异无统计学意义(P=0.058);模型组和实验组总胆固醇(total cholesterol,TC)和低密度脂蛋白-胆固醇(low-density lipoprotein cholesterol,LDL-C)明显增加,与对照组相比差异具有统计学意义(P=0.000);模型组和实验组相比,TC和LDL-C差异也有统计学意义(P=0.000和0.002);模型组和实验组大鼠ET-1、NO、EL与对照组相比差异均有统计学意义(P=0.000),与模型组相比,实验组NO水平升高,ET-1、EL水平降低,差异具有统计学意义(P=0.017、0.008和0.000)。结论:缬沙坦在细胞损伤期,即具有明显内皮细胞保护功能。对动脉粥样硬化患者早期用药,能够保护细胞完整性,减少凋亡发生,起到疾病预防和治疗的重要意义。

Objective ：To investigate the effect of angiotensin 11 receptor blocker on atherosclerosis aortic endothelial ceils through treating atherosclerotic rats with ARB. Methods：Totally 30 Wistar rats were randomly divided into 3 groups： model group, experiment group and control group with 10 rats in each group. Atherosclerosis rat model was established in model group by feeding high fat diet. Valsartan intervention was added in experiment group. After eight weeks, nitric oxide （NO）, endothelin （ET）, cytochrome-c （Cyt-c） and plasma endothelial lipase（EL） levels of aortic endothelial cells were compared. Results：At the end of the experiment, HE stain- ing of model group showed obvious plaque formation with a large amount of lipid infiltration. Immunohistochemical staining of Cyc-c showed that the positive rate of apoptosis of endothelial cells were higher in model group（36.85 ± 12.45） than in control group（0.81 ± 0.11 ） and experimental group（ 13.85 ± 6.41 ）（P=-0.000）. The positive rate of apoptosis of smooth muscle cells was higher than in model group（9.65 ± 2.62） than in control group（O.06 ± 0.01）（P=0.000）,but did not statistically different from that of experimental group （7.85 ± 1.34）（P=0.058）. Total cholesterol（TC） and low-density lipoprotein cholesterol（LDL-C） levels in model group and experi- mental group were increased significantly,however, did not statistically different those in control group （P=0.000）. There was statisti- cally significant difference in TC and LDL-C between model group and experimental group（P=0.000,P=0.002）. There was statistically significant difference in ET-1, NO,EL between model group, experimental group and control group （P=0.000）. There was statistically significant difference in ET-1, NO, EL between model group and experimental group（P=0.017,0.008,0.000）. Conclusion：Valsarta can protect function of endothelial cells during cell injury period. For patients with early atherosclerosis, Valsarta could protect the integri-ty of cells, reduce the apoptosis, playing a significant role in the prevention and treatment of disease.