Evidence for the role of mast cells in colon-bladder cross organ sensitization.

Evidence for the role of mast cells in colon-bladder cross organ sensitization.
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DOI:
10.1016/j.autneu.2012.09.002
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发表时间:
2013-01
影响因子:
2.7
通讯作者:
Pezzone, Michael A.
Pezzone, Michael A.
中科院分区:
医学4区
文献类型:
--
作者:
Fitzgerald, Jocelyn J.;Ustinova, Elena;Koronowski, Kevin B.;de Groat, William C.;Pezzone, Michael A.

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本研究探讨了肥大细胞在三硝基苯磺酸(TNBS-CI)刺激结肠引起的结肠-膀胱跨器官致敏中的作用。在TNBS-CI后12天的乌拉坦麻醉大鼠中,排尿间隔从357秒缩短至201秒,并且通过从膀胱腔吸收荧光素钠间接测量的尿路上皮渗透性增加了6倍。这些作用被阻断口服酮替芬(10毫克/公斤,5天),肥大细胞稳定剂。TNBS-CI在野生型小鼠中产生类似的排尿间隔缩短(从319秒至209秒)和尿路上皮渗透性增加10倍;然而,这在KitaWa/KitaW-va肥大细胞缺陷型小鼠中没有发生。由化合物48/80(50 μg/ml)(肥大细胞活化剂)引起的膀胱条的收缩反应在来自TNBS-CI大鼠的条中(基线张力增加145%)显著大于对照大鼠(增加55%)。用酮替芬(20 μM)预处理TNBS-CI大鼠的条收缩减少80-90%,而对照动物的条收缩无显著变化。用SLIGRL-NH 2(100 μM)预处理膀胱条,使肥大细胞类胰蛋白酶受体PAR-2脱敏。SLIGRL-NH 2预处理使来自TNBS-CI大鼠的条中48/80诱导的收缩减少60-80%,但不改变来自对照大鼠的条中的收缩。这些数据表明,膀胱肥大细胞有助于膀胱功能障碍后,结肠膀胱交叉致敏。
This study examined the contribution of mast cells to colon–bladder cross organ sensitization induced by colon irritation with trinitrobenzene sulfonic acid (TNBS-CI). In urethane anesthetized rats 12 days after TNBS-CI, the voiding interval was reduced from 357 s to 201 s and urothelial permeability, measured indirectly by absorption of sodium fluorescein from the bladder lumen, increased six-fold. These effects were blocked by oral administration of ketotifen (10 mg/kg, for 5 days), a mast cell stabilizing agent. TNBS-CI in wild type mice produced a similar decrease in voiding interval (from 319 s to 209 s) and a 10-fold increase in urothelial permeability; however this did not occur in KitaWa/KitaW-va mast cell deficient mice. Contractile responses of bladder strips elicited by Compound 48/80 (50 μg/ml), a mast cell activating agent, were significantly larger in strips from rats with TNBS-CI (145% increase in baseline tension) than in control rats (55% increase). The contractions of strips from rats with TNBS-CI were reduced 80–90% by pretreatment of strips with ketotifen (20 μM), whereas contractions of strips from control animals were not significantly changed. Bladder strips were pretreated with SLIGRL-NH2 (100 μM) to desensitize PAR-2, the receptor for mast cell tryptase. SLIGRL-NH2 pretreatment reduced by 60–80% the 48/80 induced contractions in strips from rats with TNBS-CI but did not alter the contractions in strips from control rats. These data indicate that bladder mast cells contribute to the bladder dysfunction following colon–bladder cross-sensitization.
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