前列腺素E受体-4在透明质酸酶诱导大鼠慢性膀胱炎中的作用

Effect of prostaglandin E2 receptor-4 on hyaluronidase-induced chronic cystitis in rats

目的 观察前列腺素E受体-4（EP4）在透明质酸酶诱导的大鼠慢性膀胱炎中的作用.方法 采用膀胱灌注透明质酸酶构建慢性膀胱炎症大鼠模型,尿流动力学检测膀胱功能,逆转录聚合酶链反应（RT-PCR）筛选EP受体mRNA表达,Western blot检测EP4受体蛋白表达,苏木素-伊红（HE）染色计算炎性细胞数量.结果 模型组炎性细胞数目为（45.3±6.9）个/视野;排尿时间间隔为（119.2±28.2）s;膀胱容量为（0.37±0.04） ml.对照组炎性细胞数目为（4.8±1.1）个/视野;排尿时间间隔为（439.3±16.8）s;膀胱容量为（1.26±0.06） ml.与对照组比较,模型组大鼠显示明显慢性炎症,排尿时间间隔缩短,膀胱容量降低,膀胱EP4受体mRNA及蛋白表达均显著升高（P＜0.05）.EP4受体拮抗剂AH23848干预后,大鼠排尿时间间隔及膀胱容量明显增加（P＜0.05）,分别为（277.3±39.1）s、（0.96 ±0.11） ml,但膀胱炎症无明显改善.结论 EP4受体在透明质酸酶诱导的慢性膀胱炎大鼠膀胱组织中表达升高,其受体拮抗剂可能可以作为临床间质性膀胱炎潜在治疗靶点.

Objective To evaluate the effect of prostaglandin E2 receptor-4 （EP4） on hyaluronidase-induced chronic cystitis in rats.Methods Chronic cystitis rat models were created by intravesical hyaluronidase.Voiding patterns were investigated by cystometrography.The mRNA levels of EP receptors were analyzed with real time reverse transcription polymerase chain reaction.The protein levels of EP4 were evaluated by Western blotting.The count of inflammatory cells was determined by hematoxylin and eosin （HE） stain.Results In model group,the count of inflammatory cells was （45.3 ±6.9） cells/field; The intercontraction intervals was （119.2 ± 28.2） s ; The bladder capacity was （0.37 0.04） ml.In control group,the count of inflammatory cells was （4.8 ± 1.1） cells/field; The intercontraction intervals was （439.3 ± 16.8） s; The bladder capacity was （1.26 ±0.06） ml.Compared with control,the rats of model group showed chronic inflammation,decreased intereontraction intervals and bladder capacity,and the mRNA and protein levels of EP4 increased significantly （all P ＜ 0.05）.After administration of EP4 antagonist AH23848,both intercontraction intervals and bladder capacity increased significantly （both P ＜0.05）.And they were （277.3 ± 39.1） s,（0.96 ± 0.11） ml,respectively.But the inflammation did not reduce.Conclusion The expression of EP4 receptor increased in the bladder of hyaluronidase-induced chronic cystitis.And its antagonist may act as the potential therapeutic target.