Tyagi Pradeep, Chancellor Michael, Yoshimura Naoki, Huang Leaf
Department of Pharmaceutical sciences, School of Pharmacy, University of Pittsburgh, PA, USA.
BJU Int. 2008 Mar;101(5):627-32. doi: 10.1111/j.1464-410X.2007.07334.x. Epub 2007 Dec 5.
To evaluate the effect of liposomes prepared from various natural and synthetic lipids in a rat bladder injury model in the absence or the presence of cholesterol and to elucidate the key structural elements necessary for the efficacy of liposomes required for alleviating bladder hyperactivity.
The intravesical pressure was recorded using a transurethral catheter in adult female Sprague-Dawley rats anaesthetized with urethane (1.0 g/kg subcutaneously). Continuous cystometrograms (CMGs) were obtained by slowly filling the bladder with solutions of varying compositions after obtaining a baseline CMG with saline. Rat urothelium was injured with protamine sulphate (PS) and irritated by subsequent infusion of KCl (500 mm) for 1 h. Thereafter, liposomes prepared in KCl using several natural and synthetic phospholipids were infused for 2 h. The percentage reduction in bladder contraction frequency (BCF) was used as a comparative variable for judging the activity of different phospholipids.
Exposure of rat bladder to sequential infusion of PS and KCl increased its BCF and empty liposomes of uncharged zwitterionic phospholipids markedly attenuated the PS-induced irritation and decreased the raised BCF. But empty liposomes prepared with either cationic or anionic charged lipids were not able to achieve the same effect. Addition of cholesterol did not significantly increase their efficacy. Optimal efficacy of liposomes was achieved with phosphatidylcholines with longer acyl chains and saturation in only one of the two acyl chains.
These in vivo studies show that phospholipids attenuate the bladder irritation from KCl after PS-induced bladder injury.
评估在不存在或存在胆固醇的情况下，由各种天然和合成脂质制备的脂质体对大鼠膀胱损伤模型的影响，并阐明减轻膀胱活动亢进所需脂质体发挥功效的关键结构要素。
在经氨基甲酸乙酯（1.0 g/kg皮下注射）麻醉的成年雌性Sprague-Dawley大鼠中，使用经尿道导管记录膀胱内压。在用生理盐水获得基线膀胱测压图（CMG）后，通过用不同成分的溶液缓慢充盈膀胱来获取连续膀胱测压图。用硫酸鱼精蛋白（PS）损伤大鼠膀胱上皮，随后注入KCl（500 mmol）1小时进行刺激。此后，将在KCl中使用几种天然和合成磷脂制备的脂质体注入2小时。膀胱收缩频率（BCF）的降低百分比用作判断不同磷脂活性的比较变量。
大鼠膀胱先后接受PS和KCl灌注后，其BCF增加，而由不带电荷的两性离子磷脂制成的空脂质体显著减轻了PS诱导的刺激，并降低了升高的BCF。但是，用带阳离子或阴离子电荷的脂质制备的空脂质体无法达到相同的效果。添加胆固醇并未显著提高其功效。酰基链较长且仅在两条酰基链中的一条上饱和的磷脂酰胆碱能使脂质体达到最佳功效。
这些体内研究表明，磷脂可减轻PS诱导的膀胱损伤后KCl引起的膀胱刺激。
