α-1AR亚型拮抗剂对膀胱出口梗阻大鼠排尿的影响

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目的探讨α-1AR亚型拮抗剂缓解膀胱出口梗阻患者膀胱刺激症状的机理。方法利用连续排尿记录系统(CMRS)测定51只SD大鼠排尿频率准值,建立膀胱出口梗阻(BOO)(n=40),对照组行假手术(n=11)。6周后测定大鼠排尿频率,并通过皮下植入渗透性缓释泵分别给于5MU、坦索罗辛及对照溶剂,治疗1周后再次测定大鼠排尿频率,同时测定α-1AR激动剂苯肾上腺素对大鼠动脉血压的影响。观察α-1aAR拮抗剂5MU和α-1a/α-1dAR拮抗剂坦索罗辛对膀胱出口梗阻大鼠排尿频率的影响。结果BOO组膀胱平均重量为对照组重量的4.9倍(663±88vs136±15mg,P<0.001)。BOO组膀胱重量>500mg的大鼠排尿频率明显增加(11.2±8.7)次,膀胱重量<255mg的大鼠排尿频率相应减少(9.7±3.2)次,两组相比差异有统计学意义(P=0.01)。膀胱重量>500mg大鼠中,坦索罗辛明显降低了其排尿频率(减少23.13±10.86次),与注射对比溶剂组比较差异有统计学意义(P=0.026);但5MU治疗无效。坦索罗辛和5MU均可抑制苯肾上腺素对大鼠动脉血压的作用。结论膀胱重量>500mg的BOO大鼠排尿频率明显增高,α-1a/α-1d联合受体拮抗剂坦索罗辛降低BOO大鼠排尿频率的作用明显强于5MU。 Objective To investigate the mechanism of a-1AR subtype antagonist in relieving bladder irritation in patients with bladder outlet obstruction. Methods The urinary frequency of 51 SD rats was determined by continuous urinary recording system (CMRS). The bladder outlet obstruction (BOO) was established (n = 40). The control group was sham operated (n = 11). After 6 weeks, the frequency of micturition in rats was measured. The 5MU, tamsulosin and control solvent were administered subcutaneously with osmotic slow-release pump. After 1 week of treatment, the frequency of urination in rats was measured again. The α-1AR agonist Effect of Phenylephrine on Arterial Blood Pressure in Rats. To observe the effects of α-1aAR antagonist 5MU and α-1a / α-1dAR antagonist tamsulosin on micturition frequency in bladder outlet obstruction rats. Results The average weight of bladder in BOO group was 4.9 times that of control group (663 ± 88 vs 136 ± 15 mg, P <0.001). The voiding frequency of rats with BOO> 500mg significantly increased (11.2 ± 8.7), and the frequency of voiding of rats with bladder <255mg decreased significantly (9.7 ± 3.2). There was significant difference between the two groups (P = 0.01). Tamsulosin significantly reduced the micturition frequency (23.13 ± 10.86 times) in bladder weight> 500 mg rats, and there was significant difference between the two groups (P = 0.026); however, 5MU treatment was ineffective. Tamsulosin and 5MU can inhibit the phenylephrine on the role of arterial blood pressure in rats. Conclusion The voiding frequency of BOO rats with bladder weight> 500mg was significantly increased. The effect of tamsulosin combined with α-1a / α-1d antagonist tamsulosin on urination frequency of BOO rats was significantly stronger than that of 5MU.
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