目的 探讨海藻酸抗动脉粥样硬化(AS)的作用及其机制.方法 将2年龄雄性Wistar大鼠60只随机分成对照组、模型组、治疗组、阳性组.对照组喂食普通饲料,其他各组喂食高脂饲料,并一次性腹腔注射维生素D340万IU/kg.1 0周后处死对照组和模型组大鼠各10只,进行造模指标检测和病理学观察.各组所余1 0只大鼠继续喂养,对照组和模型组每日1次子生理盐水10 mL/kg灌胃,治疗组和阳性组每日1次分别予海藻酸0.6 g/kg和普罗布考0.02 g/kg灌胃治疗.10周后处死各组大鼠,应用RT-PCR技术检测超氧化物歧化酶(SOD)、一氧化氮合成酶(NOS)、高密度脂蛋白(HDL)和细胞间黏附分-1(ICAM-1)的基因表达,用流式细胞术检测内皮细胞的凋亡率.结果 造模1 0周后,模型组大鼠的主动脉病变评分明显升高(P＜0.01),光镜下为典型的AS斑块形成.治疗10周后,治疗组的AS斑块消退,内膜光滑无红染,评分明显低于模型组(P＜0.01).治疗组大鼠的SOD、NOS、HDL基因表达明显上调,ICAM-1基因表达明显下调,内皮细胞凋亡率明显下降,与模型组比较,差异有统计学意义(P＜0.01).治疗组大鼠一氧化氮的生成明显升高,丙二醛和非对称二甲基精氨酸的生成都明显减少.结论 海藻酸通过促进SOD、NOS、HDL的基因表达和抑制内皮细胞的凋亡,而清除自由基、改善内皮细胞功能,发挥抗AS的作用.%Objective To discuss the effect and mechanism of alginic acid in therapy of the anti-atherosclerosis. Methods Sixty two-year-old Wistar rats were divided randomly into control group, model group, therapeutic group and positive group. The control group was fed with normal forage, and other groups were fed with high fat forage and intraperitoneal injected with Vitamin D3 4X105 IU/kg. Ten weeks later, 10 rats in control group and model group were killed to detect relevant indicators. Then based on normal breeding, the control group and model group were fed with NS 10 Ml/kg, the therapeutic group was fed with alginic acid 0.6 g/kg, the positive group was fed with probucol 0.02 g/kg every day. Ten weeks later, RT-PCR was used to detect the genes expression of SOD, NOS, HDL and ICAM-1, and the rate of apoptosis of the endothelial cells was measured by flow cytometry. Results After the model made 10 weeks, the pathologic level of artery increased significantly (P<0.01), presenting AS-curved speckle. Ten weeks after therapy, the AS-curved speckle of the rapeutic group disappeared obviously compared with the model group (P< 0.01). The genes expression of SOD, NOS, HDL were obviously up-regulated, while the gene expression of ICAM-1 was down-regulated, the rate of apoptosis decreased significantly (P<0.01). The contents of NO increased obviously, the contents of Asymmetrical dimethyl arginine (ADMA), ET-1 and TNF-a decreased significantly. Conclusion Alginic acid can promote the genes expression of SOD, NOS, HDL and inhibit the apoptosis of endothelial cell, then clean free radicals, restore and improve the function of endothelial cells effectively, inhibit the AS generation significantly.
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