Lutton C, Milliat F, Feurgard C, Mathe D, Aigueperse J, Meslin J C
Laboratoire de Physiologie de la Nutrition, Unité Associée Université Paris Sud XI/INRA, Orsay, France.
Int J Radiat Biol. 1999 Feb;75(2):175-81. doi: 10.1080/095530099140627.
To investigate regional cholesterol synthesis and kinetics following whole-body gamma-irradiation in the genetically hypercholesterolaemic RICO rat.
Male RICO rats were fed a semi-purified diet for 1 month. At 10 weeks old they were exposed to gamma-irradiation (4 Gy, 1.5 Gy/min) together with controls. At intervals from 1-8 days after irradiation an intraperitoneal administration of [1-14C] acetate was given in order to estimate cholesterogenesis in mucosal cells located at different sites in the small intestine. The protein and DNA contents of the different enterocytes isolated along the crypt/villus axis in four equal parts of the intestine were also determined.
A marked decrease of the mean quantities of cholesterol, DNA or protein in mucosa was seen 1 and 2 days after irradiation, showing the loss of 30-40% of the intestinal epithelium. An overshoot of the cell amount was observed after 4 days with a return to basal values by 8 days after irradiation. The kinetic and topological evolution of cholesterol radioactivity, which reflects in situ cholesterol synthesis, showed a typical gradient in controls and at 8 days after irradiation. Cholesterogenesis decreased from the first to the third quarter of the small intestine (duodenum to proximal ileum), and then increased in the fourth quarter (distal ileum). In all segments of the small intestine, cholesterogenesis decreased from crypt cells to villus tip. At days 1 and 2 the gradient of cholesterogenesis on the villus was abolished. A slow recovery was seen from day 4 with a strong overshoot of cholesterol synthesis in crypt cells in every part of the small intestine.
The RICO rat is a useful model for studying the effect of irradiation on regional cholesterogenesis in intestinal mucosa. Cholesterol synthesis in crypt cells was lowered 1 and 2 days after irradiation, over-expressed after 4 days and subsequently returned to its normal level.
研究遗传性高胆固醇血症RICO大鼠全身γ射线照射后局部胆固醇合成及动力学变化。
雄性RICO大鼠喂食半纯化饮食1个月。10周龄时，它们与对照组一起接受γ射线照射（4 Gy，1.5 Gy/分钟）。在照射后1至8天的不同时间间隔，腹腔注射[1-14C]乙酸盐，以估计位于小肠不同部位的黏膜细胞中的胆固醇生成。还测定了沿小肠隐窝/绒毛轴四个等份分离的不同肠上皮细胞的蛋白质和DNA含量。
照射后1天和2天，黏膜中胆固醇、DNA或蛋白质的平均含量显著下降，表明肠上皮细胞损失了30-40%。4天后观察到细胞数量的过度增加，照射后8天恢复到基础值。反映原位胆固醇合成的胆固醇放射性的动力学和拓扑演变在对照组和照射后8天显示出典型的梯度。胆固醇生成从十二指肠到回肠近端的小肠第一季度到第三季度下降，然后在第四季度（回肠远端）增加。在小肠的所有节段中，胆固醇生成从隐窝细胞到绒毛顶端逐渐下降。在第1天和第2天，绒毛上胆固醇生成的梯度消失。从第4天开始出现缓慢恢复，小肠各部位隐窝细胞中的胆固醇合成强烈过度增加。
RICO大鼠是研究辐射对肠黏膜局部胆固醇生成影响的有用模型。照射后1天和2天，隐窝细胞中的胆固醇合成降低，4天后过度表达，随后恢复到正常水平。
