【摘要】 目的:研究氧氟沙星对大鼠结肠上皮细胞分泌Cl-的影响,探讨氧氟沙星引起腹泻的机制。方法:在结肠黏膜上皮基底侧膜侧分别加入0.1mmol/L~6mmol/LOFLX,观察OFLX对大鼠结肠黏膜短路电流的影响;运用多种工具药或改变溶液中相关离子的浓度研究氧氟沙星对结肠上皮细胞离子转运的影响。结果:在结肠黏膜的基底侧膜侧加入氧氟沙星(0.1~6mmol/L),引起剂量依赖性的短路电流升高,EC50=2.024mmol/L(每一浓度点的n=6)。在结肠黏膜的顶端膜侧加入Na+通道阻断剂阿米洛利(10μmol/L),对氧氟沙星引起的短路电流变化无影响(n=6,P>0.05);加入Cl-通道阻断剂diphenylamine-2-carboxylicacid(1mmol/L)可完全阻断氧氟沙星引起的短路电流升高(n=6,P<0.001);将Cl-从溶液中替换掉,抑制了该短路电流变化的45%(n=4,P<0.05);将HCO3-从溶液中替换掉,氧氟沙星引起的短路电流变化无明显改变(n=6,P>0.05);结肠黏膜的两侧预先加入碳酸酐酶抑制剂乙酰唑胺(1mmol/L),对氧氟沙星在结肠上皮产生的效应无显著影响(n=5,P>0.05);在结肠上皮的基底侧膜侧加入Na+-K+-2Cl-共转运体的阻断剂布美他尼(100μmol/L),氧氟沙星引起的短路电流变化被抑制了60%(n=5,P<0.05),加入非选择性K+通道阻断剂Ba2+(1mmol/L)则完全抑制了氧氟沙星在结肠黏膜产生的短路电流变化(n=6,P<0.01)。结论:氧氟沙星具有促进大鼠结肠黏膜分泌Cl-的作用。提示氧氟沙星导致腹泻的机制可能与其引起的结肠黏膜分泌Cl-有关。更多还原

【Abstract】 Aim: To investigate the effects of ofloxacin on rat distal colonic mucosa secreating Cl - .Methods:OFLX at different concentrations （0.1 mmol/L⁶ mmol/L） was added to the rat distal colonic mucosa,respectively to observe the changes of the short GAAB2 circuit current（I sc ）;different tool agents were added respectively to observe the change of I sc .Results:Basolateral addition of ofloxacin （0.1 mmol/L～6 mmol/L, n= 6 for all concentrations） elicited a concentration-dependent I sc increase. EC 50 was about 2.024 mmol/L; apical application of Na + channel blocker, amiloride（10 μmol/L） did not significantly affect the ofloxacin-induced changes in I sc （ n= 6, P> 0.05）. The Cl - -channel blocker, diphenylamine-2-carboxylic acid （1 mmol/L, apical） completely inhibited the ofloxacin-induced changes in I sc （n=6, P < 0.001）. Removal of external Cl - decreased the response by 45%（ n=4 , P<0.05）. Removal of HCO₃ - from buffer solution did not affect the ofloxacin-induced changes in I sc significantly（n=6, P>0.05）. Pretreatment of the colonic mucosa with the carbonic anhydrase inhibitor, acetazolamide（1 mmol/L,both sides） did not alter the ofloxacin-induced changes in I sc （n=5, P> 0.05 ）. Pretreatment with bumetanide（100 μmol/L, basolateral）, a blocker of Na +-K +-2Cl - -cotransport, significantly reduced the ofloxacin-induced changes in I sc by 60% （ n= 5, P<0.05）. The ofloxacin-induced change in I sc was almost completely inhibited by basolateral exposure to Ba 2+ （1 mmol/L）,a nonspecific K + channel blocker（n=6, P< 0.01 ）. Conclusion: The ofloxacin could stimulate rat colonic mucosa to secrete Cl - ,which might be related to the diarrhea induced by ofloxacin in clinic.更多还原