Dupont J, Lumb W V, Nelson A W, Seegmiller J P, Hotchkiss D, Chase H P
Atherosclerosis. 1985 Dec;58(1-3):205-22. doi: 10.1016/0021-9150(85)90067-x.
Since 1973 the portacaval shunt has been used as a treatment for homozygous familial hypercholesterolemia. Favorable results have been reported, but the mechanism or reduction of cholesterol is not clear. The objective of this research was to evaluate mechanisms of lipid alterations after portacaval shunting in Yucatan miniature swine. The animals were fed a high-fat diet, similar in composition to the average American diet, with or without added cholesterol. Controls were fed the atherogenic diet (+ cholesterol) for 8 months. Pigs were fed atherogenic or American diets for 8 months, then surgery (shunt or sham) was performed. They were continued on the diets for another 8 months. The vascular system was examined for the distribution and severity of atherosclerotic disease. Blood lipids and numerous biochemical indices were measured. Progression of atherosclerosis was slowed by portacaval shunting. Low density lipoprotein (LDL) concentrations were positively and high density lipoprotein (HDL) concentrations were negatively correlated with severity of atherosclerosis. Serum insulin concentrations were positively correlated with atherosclerosis. Cholesterol synthesis was increased by the shunting and decreased by cholesterol feeding. The cholesterol-fed swine is not an adequate model for familial hypercholesterolemia, but the results are consistent with inhibition of the atherosclerotic process and the involvement of lipoproteins and insulin in the mechanisms.
自1973年以来,门腔分流术一直被用作纯合子家族性高胆固醇血症的一种治疗方法。已有报道称取得了良好效果,但胆固醇降低的机制尚不清楚。本研究的目的是评估尤卡坦小型猪门腔分流术后脂质改变的机制。给动物喂食高脂肪饮食,其成分与普通美国饮食相似,添加或不添加胆固醇。对照组喂食致动脉粥样硬化饮食(+胆固醇)8个月。猪先喂食致动脉粥样硬化或美国饮食8个月,然后进行手术(分流或假手术)。之后它们继续食用这些饮食8个月。检查血管系统中动脉粥样硬化疾病的分布和严重程度。测量血脂和众多生化指标。门腔分流术减缓了动脉粥样硬化的进展。低密度脂蛋白(LDL)浓度与动脉粥样硬化严重程度呈正相关,高密度脂蛋白(HDL)浓度与动脉粥样硬化严重程度呈负相关。血清胰岛素浓度与动脉粥样硬化呈正相关。分流术使胆固醇合成增加,而喂食胆固醇则使其减少。喂食胆固醇的猪不是家族性高胆固醇血症的合适模型,但结果与动脉粥样硬化进程的抑制以及脂蛋白和胰岛素在该机制中的作用一致。