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Obstructive cholestasis alters intestinal transit in mice: role of opioid system.

机译:阻塞性胆汁淤积症改变小鼠的肠道运输:阿片样物质系统的作用。

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Acute cholestasis is associated with increased activity of the endogenous opioid system. It is also known that opioid receptor agonists like morphine decrease the intestinal transit. The purpose of the present study was to investigate the effect of cholestasis on the small intestine transit and the possible involvement of opioid system in this phenomenon in mice. Cholestasis was induced by bile duct-ligation and intestinal transit was measured with charcoal meal and calculation of percent of transit through small intestine. The effect of chronic administration of naltrexone and acute pretreatment with morphine on intestinal transit was evaluated in bile duct-ligated (BDL) as well as unoperated (CTL) and sham-operated (SHAM) animals. The plasma alkaline phosphatase and alanine aminotransferase activities were also measured. A significant decrease in small intestine transit (%transit) was observed in BDL mice compared to SHAM animals, which was prominent even after 24 h of cholestasis. Chronic pretreatment with an opioid receptor antagonist, naltrexone, (10 mg/kg, i.p for 2, 4 or 6 days) completely restored the cholestasis-induced decrease in %transit to that of control animals. Although the acute administration of morphine (2 mg/kg, s.c.) 20 min before charcoal feeding caused a significant decrease in the intestinal transit of CTL and SHAM animals, it did not decrease the %transit of BDL animals on the day 5 after operation. Our findings show that acute cholestasis is associated with a prominent decrease in small intestine transit in mice and opioid receptors maybe involved in this phenomenon.
机译:急性胆汁淤积症与内源性阿片样物质系统的活性增加有关。还已知阿片受体激动剂(如吗啡)会减少肠道运输。本研究的目的是研究胆汁淤积对小鼠小肠运输的影响以及阿片样物质系统可能与这种现象有关。胆管结扎可引起胆汁淤积,用木炭粉测定肠运输,并计算通过小肠的运输百分比。在胆管结扎(BDL)以及未手术(CTL)和假手术(SHAM)的动物中评估了慢性给予纳曲酮和急性吗啡预处理对肠道运输的影响。还测量了血浆碱性磷酸酶和丙氨酸氨基转移酶的活性。与SHAM动物相比,BDL小鼠的小肠转运(%transit)显着减少,即使在胆汁淤积24小时后也很明显。用阿片受体拮抗剂纳曲酮(10 mg / kg,腹腔注射持续2天,4天或6天)进行慢性预处理,可以完全恢复胆汁淤积症诱发的相对于对照动物的%转运。尽管在喂食木炭前20分钟急性给予吗啡(2 mg / kg,皮下注射)使CTL和SHAM动物的肠道转运明显减少,但并没有降低术后5天BDL动物的转运百分比。我们的发现表明,急性胆汁淤积症与小鼠小肠运输的显着减少有关,而阿片受体可能参与了这种现象。

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