小鼠胆汁淤积性瘙痒中KATP通道的可能参与

IF 1.3 Q3 PHARMACOLOGY & PHARMACY
Arya Afrooghe, Maryam Shayan, Nazgol-Sadat Haddadi, Asma Rashki, Shahabaddin Solaimanian, Maryam Shokrian Zeini, Ahmad-Reza Dehpour
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引用次数: 0

摘要

胆汁淤积性瘙痒严重损害患者的生活质量;然而,治疗的选择是有限的,远远不够。atp敏感钾通道(KATP通道)有助于传递信号,包括瘙痒。在此,我们研究了KATP通道在胆管结扎(BDL)引起的小鼠胆汁淤积性瘙痒中的作用。在BDL和假手术(Sham)小鼠中通过腹腔给药KATP通道打开剂(二氮和米诺地尔)和阻滞剂(格列本脲)。裸场试验结束后,对皮内车辆注射后的抓痕行为进行1小时的录像。我们通过RT-qPCR分析研究了编码KATP通道的基因(Kcnj8和Kcnj11)在皮肤表达中的可能变化。我们检测到胆汁淤积小鼠在皮内注射时抓挠反应增加,这代表了胆汁淤积性瘙痒。KATP通道开放剂、二氮氧化合物(10mg /kg, i.p)和米诺地尔(10mg /kg, i.p)可减轻胆管结扎小鼠的抓伤反应。另一方面,KATP通道阻滞剂格列本脲(3mg /kg, i.p)加剧了抓伤行为。此外,用亚有效剂量的格列苯脲(1mg /kg, i.p)预处理可以逆转二氮氧化合物(10mg /kg, i.p)和米诺地尔(10mg /kg, i.p)的止痒作用。野外实验显示,运动活动对抓痕行为没有影响。我们的RT-qPCR分析也显示Kcnj11在BDL小鼠中的表达增加。我们得出结论,KATP通道可能参与胆汁淤积性瘙痒。需要进一步的研究来阐明胆汁淤积和瘙痒之间的其他联系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The possible involvement of KATP channels in cholestatic pruritus in mice

Cholestatic itch dramatically impairs the quality of life of affected patients; however, the therapeutic choices are limited and far from sufficient. ATP-sensitive potassium channels (KATP channels) contribute to transmitting signals, including itch. Here, we investigated the role of KATP channels in cholestatic pruritus in mice induced by bile duct ligation (BDL). KATP channel openers (diazoxide and minoxidil) and blockers (glibenclamide) were administered via the intraperitoneal route in BDL and sham-operated (Sham) mice. After the open-field test, the scratching behavior in response to the intradermal vehicle injection was videotaped for one hour. We investigated the probable alterations in the dermal expression of genes encoding the KATP channel (Kcnj8 and Kcnj11) via RT-qPCR analysis. We detected increased scratching responses in cholestatic mice regarding intradermal vehicle injection, representing cholestatic pruritus. KATP channel openers, diazoxide (10 mg/kg, i.p.), and minoxidil (10 mg/kg, i.p.) attenuated scratching responses in the bile duct ligated mice. On the other hand, KATP channel blocker glibenclamide (3 mg/kg, i.p.) intensified the scratching behavior. Moreover, pre-treatment with the sub-effective dose of glibenclamide (1 mg/kg, i.p.) reversed the anti-pruritic effects of diazoxide (10 mg/kg, i.p.) and minoxidil (10 mg/kg, i.p.). The open-field test revealed that the scratching behavior was not affected by locomotor activity. Our finding of RT-qPCR analysis also showed an increase in the expression of Kcnj11 in BDL mice. We conclude that KATP channels are possibly involved in cholestatic itch. Further studies are needed to elucidate the other associations between cholestasis and itch.

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来源期刊
Advances in Traditional Medicine
Advances in Traditional Medicine PHARMACOLOGY & PHARMACY-
CiteScore
4.30
自引率
0.00%
发文量
50
期刊介绍: Advances in Traditional Medicine (ADTM) is an international and peer-reviewed journal and publishes a variety of articles including original researches, reviews, short communications, and case-reports. ADTM aims to bridging the gap between Traditional knowledge and medical advances. The journal focuses on publishing valid, relevant, and rigorous experimental research and clinical applications of Traditidnal Medicine as well as medical classics. At the same time, the journal is devoted to communication among basic researcher and medical clinician interested in the advancement of Traditional Medicine. Topics covered by the journal are: Medical Classics & History; Biomedical Research; Pharmacology & Toxicology of Natural Products; Acupuncture & Moxibustion; Sasang Constitutional Medicine; Diagnostics and Instrumental Development; Clinical Research. ADTM is published four times yearly. The publication date of this journal is 30th March, June, September, and December.
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