目的探讨乙酰半胱氨酸(N-acetylcysteine,NAC)对硫酸鱼精蛋白(protamine sulfate,PS)诱导的大鼠膀胱炎的治疗作用及可能机制。方法雌性SD大鼠64只,按随机数字表法分为生理盐水灌注组(NS组)、硫酸鱼精蛋白灌注组(Ps组)、Ns+Ps组、NAC+Ps组,每组16只。NS组0.5mL生理盐水灌入膀胱并在膀胱内保留30min。PS组采用0.5mL、30mg/mLPS灌注大鼠膀胱,方法同Ns组。Ns+Ps组和NAC+Ps组大鼠在膀胱灌注Ps前2h,经腹腔注射0.5mLNS或0.5mL300mg/kgNAC溶液,灌注方法同Ns组。各组大鼠每周处理3次,持续1个月。病理染色及膀胱湿质量检测分析大鼠膀胱炎症、水肿及肥大细胞浸润改变;尿动力学检测大鼠尿动力各项指标;Westernblot法检测大鼠膀胱炎症因子IL-6和TNF-α表达。结果NAC治疗组大鼠膀胱尿动力指标[收缩间歇(330.024±69.49)s]、膀胱黏膜损伤指数(1.37±0.91)及肥大细胞浸润计数(1.93±1.34)均优于Ps灌注组尿动力指标[收缩间歇(161.32±58.17)s]、膀胱黏膜损伤指数(2.75±0.46)及肥大细胞浸润计数(3.40±2.19),Western blot法检测显示NAC治疗组较Ps灌注组炎症因子IL-6和TNF-α表达也降低(P〈0.01)。结论NAC可显著改善PS诱导的大鼠膀胱炎,其机制可能是降低PS诱导的膀胱炎TNF-α和IL-6的表达,以及减少肥大细胞浸润。
Objective To determine the therapeutic effect of N-acetylcysteine (NAC) in the treatment of protamine sulfate (PS) -induced cystitis model in rats. Methods A total of 64 female SD rats were randomly divided into normal saline (NS) infusion group, PS infusion group, PS infusion + NS treatment group, PS infusion + NAC treatment group, with 16 rats in each group. NS or 300 mg/kg NAC solution of 0.5 mL was intra-peritoneally injected to the rats from the 2 treatment groups. In 2 h later, NS or 30 mg/mL NS of 0.5 mL were poured into the rat bladder from the infusion groups and then preserved in the bladder for 30 min. All rats were treated 3 times every week for a month. Rat urodynamic urodynamic test, HE staining and bladder wet weight was used to measure rat bladder inflammation index, edema and mast cell infiltration. Western blotting was used to detect the expression of rat bladder inflammatory cytokines TNF-ct and IL-6. Results NAC treatment resulted in better urodynamic parameters ( contraction intermittence 330. 02 ± 69.49 s), bladder inflammation index ( 1.37 ±0.91 ) , and infiltrated mast cells ( 1.93 ± 1.34) when compared with PS infusion group (161.32 ± 58.17 s, 2.75 ± 0.46, 3.40 ± 2.19, P 〈 0.01 ). Western blotting showed the expression of TNF-α and IL-6 was also reduced in the bladder of NAC treatment group ( P 〈 0.01 ). Conclu sion NAC can attenuate PS-induced cystitis in rats, which may be due to its reducing the mast cell infiltration and downregulating TNF-α and IL-6.