低剂量内毒素损伤对肝细胞有机阳离子转运器表达的影响

目的 探讨低剂量内毒素(endotoxin,ET)损伤时大鼠肝细胞有机阳离子转运器(organic cat-ion transporter,OCT1)表达改变及地塞米松预处理ET损伤后OCT1表达的影响。方法 采用原位杂交技术观察ET损伤后肝细胞OCT1表达变化及用地塞米松干预ET损伤大鼠后OCT1的变化。结果 低剂量ET损伤后大鼠肝细胞超微结构出现不同程度的损伤,以16h时最低(0.5745±0.012,P<0.01);低剂量ET 地塞米松损伤后肝细胞OCT1的表达逐渐下降,在损伤后16h时降至最低(0.6327±0.007,P<0.01),其后各时相点肝细胞中OCT1 mRNA的表达又逐渐有所回升,但均较正常水平低(0.6607±0.005);地塞米松干预后,ET损伤的大鼠肝细胞中OCT1的表达在各时相点都有不同程度增加。结论 低剂量ET在没有导致肝细胞结构明显破坏之前就可以抑制肝细胞中OCT1 mRNA的转录;糖皮质激素不能使正常肝细胞OCT1 mRNA转录增加,但是可以减弱ET损伤后肝细胞OCT1 mRNA转录的抑制。

Study of the effect of the low dosage endotoxin damage on the expression of the organic cation transporter (OCT1) mRNA in hepatocytes

OBJECTIVE: To elucidate the effect of the low dosage endotoxin damage on the expression of the organic cation transporter 1 (OCT1) mRNA in hepatocytes and make an approach to the probable effect of dexamethasone on the expression of the OCT1 mRNA after endotoxin damage. METHODS: (1) The endotoxin damage model was established in rats; (2) The change of the expression of OCT1 mRNA in hepatocytes after endotoxin damage was observed by in situ hybridization method; (3) The change of the ultra structure of hepatocytes after endotoxin damage was observed with the electron microscope; (4) Dexamethasone was injected intraperitoneally before endotoxin damage in order to determine the influence of dexamethasone on the expression of OCT1 mRNA after endotoxin treatment. RESULTS: The expression of OCT1 mRNA decreased until 16 hours (0.5745+/-0.012, P<0.01) after endotoxin treatment and then increased after this time point, which was still lower than the normal control; The expression of OCT1 mRNA in rat hepatocytes increased at each time point after endotoxin damage with dexamethasone treatment. It was highest at 16 hours (0.6327+/-0.007, P<0.01) after endotoxin damage, but it was still lower than that of the normal control. CONCLUSION: Endotoxin could repress the expression of OCT1 mRNA even before the low dosage endotoxin inducing serious damage to the structure of hepatocytes; Dexamethasone could not induce the expression of OCT1 mRNA in normal hepatocytes, but could lighten the repression of endotoxin on the expression of OCT1 mRNA. And then the expression of OCT1 mRNA could increase at some extent after endotoxin damage with dexamethasone treatment.