Differential Effect of Acute Hepatic Failure on in Vivo and in Vitro P-Glycoprotein Functions in the Intestine
Differential Effect of Acute Hepatic Failure on in Vivo and in Vitro P-Glycoprotein Functions in the Intestine
复制标题
急性肝衰竭对体内和体外 P-糖蛋白小肠功能的差异影响
作者：
R. Yumoto;T. Murakami;M. Takano
目的。观察了四氯化碳诱导的大鼠急性肝衰竭（AHF）时肠道P-糖蛋白（P-gp）的表达及其功能。
方法. P-gp的表达，在体内吸收和P-gp底物（地高辛和罗丹明123），并在体外外排转运这些P-gp底物进行了研究，在不存在和存在的P-gp抑制剂（维拉帕米或环孢菌素A）使用的控制和AHF大鼠小肠的远端区域。
结果Western blot分析显示，肠P-gp表达水平保持不变，而是增加，在AHF。在体内肠P-gp功能显着降低，在AHF，作为评估的P-gp底物的吸收和解吸。相比之下，在体外P-gp功能显着较高的AHF，通过外排转运的P-gp底物通过外翻的肠。总的来说，在体内和体外条件下，AHF对肠道P-gp功能的影响不同。
结论. AHF患者体内肠P-gp功能受到抑制，这不能从体外功能研究或P-gp表达水平预测。AHF大鼠血浆中存在内源性P-gp抑制剂可能解释了体内和体外结果之间的差异。
AbstractPurpose. The expression and function of P-glycoprotein (P-gp) in the intestine in carbon tetrachloride-induced acute hepatic failure (AHF) were evaluated in rats.
Methods. The expression of P-gp, in vivo absorption and exsorption of P-gp substrates (digoxin and rhodamine 123), and in vitro efflux transport of these P-gp substrates were studied in the absence and presence of a P-gp inhibitor (verapamil or cyclosporin A) using the distal region of small intestine of control and AHF rats.
Results. Western blot analysis revealed that intestinal P-gp expression level remained unchanged, or rather increased, in AHF. The in vivo intestinal P-gp function was significantly lower in AHF, as evaluated by the absorption and exsorption of P-gp substrates. In contrast, in vitro P-gp function was significantly higher in AHF, as evaluated by the efflux transport of P-gp substrates across the everted intestine. Collectively, the intestinal P-gp function was differently affected by AHF between in vivo and in vitro conditions.
Conclusions. The in vivo intestinal P-gp function was suppressed in AHF, which could not be predicted from in vitro functional studies nor from P-gp expression level. The discrepancy between in vivo and in vitro results may be explained by the presence of endogenous P-gp inhibitors in the plasma of AHF rats.
DOI：
10.1152/ajpgi.2000.279.6.g1188
发表时间：
2000-12
期刊：
American journal of physiology. Gastrointestinal and liver physiology
影响因子：
--
作者：
H. C. Walters;A. Craddock;H. Fusegawa;M. Willingham;P. Dawson
通讯作者：
H. C. Walters;A. Craddock;H. Fusegawa;M. Willingham;P. Dawson
影响因子：
10.8
作者：
Benet, LZ;Izumi, T;Wacher, VJ
通讯作者：
Wacher, VJ