Nezami Behtash Ghazi, Talab Saman Shafaat, Emami Hamed, Assa Solmaz, Rasouli Mohammad Reza, Asadi Shahrzad, Tavangar Seyed Mohammad, Dehpour Ahmad Reza
Basic Medical Sciences Research Center, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Ann Plast Surg. 2009 Nov;63(5):558-63. doi: 10.1097/SAP.0b013e31818d458e.
Recent studies suggest a detrimental role for long-term opioid receptor stimulation in different tissues. In this study, we investigated the effect of chronic over production of endogenous opioids on skin tolerance to ischemia in a rat model of cholestasis. Sixty-six rats were randomly divided into 11 groups, 6 animals each. First group served as surgical control. In first experiment, 1, 2, and 3 weeks bile duct ligation (BDL) rats and SHAM-operated controls underwent random-pattern skin-flaps by elevating a caudally based dorsal flap (2 x 8 cm). BDL was performed by midline laparotomy and ligating the common bile duct under general anesthesia. Flap survival was assessed after 7 days (14-, 21-, and 28-day cholestatic rats, respectively). In another experiment, the first effective duration of BDL on flap survival (21 days) was chosen to receive either chronic (20 mg/kg/day) or acute (20 mg/kg, 30 minutes before flap surgery) intraperitoneal naltrexone (NTX). In the first experiment, flap survival was 56.6% +/- 2.6% (mean +/- SEM) in control group and 50.2% +/- 3.9%, 37.4% +/- 3.4%, and 35.4% +/- 6.9% in groups of 14-, 21-, and 28-day cholestatic rats, which were significantly impaired in 21- and 28-day group. In the second experiment, skin flap survival was completely reversed to their SHAM control level after chronic and acute NTX treatment (63.6% +/- 7.6% and 61.9% +/- 5.6% vs. 55.1% +/- 4.2% and 54.9% +/- 4.3%, respectively, P < 0.05). Chronic cholestasis (longer than 2 weeks) decreases the skin flap survival, which is reversed by systemic NTX. This study provides evidence, for the first time, that long-term elevated opioidergic tone impairs the skin tolerance to ischemia.
近期研究表明，长期刺激阿片受体在不同组织中具有有害作用。在本研究中，我们在胆汁淤积大鼠模型中，研究了内源性阿片类物质长期过量产生对皮肤缺血耐受性的影响。66只大鼠随机分为11组，每组6只动物。第一组作为手术对照组。在第一个实验中，1周、2周和3周胆管结扎（BDL）大鼠以及假手术对照组通过掀起基于尾部的背部皮瓣（2×8厘米）进行随机模式皮瓣手术。BDL通过中线剖腹术并在全身麻醉下结扎胆总管来进行。7天后评估皮瓣存活情况（分别为14天、21天和28天胆汁淤积大鼠）。在另一个实验中，选择BDL对皮瓣存活的首个有效持续时间（21天），给予慢性（20毫克/千克/天）或急性（20毫克/千克，皮瓣手术前30分钟）腹腔注射纳曲酮（NTX）。在第一个实验中，对照组皮瓣存活率为56.6%±2.6%（平均值±标准误），14天、21天和28天胆汁淤积大鼠组分别为50.2%±3.9%、37.4%±3.4%和35.4%±6.9%，21天和28天组显著受损。在第二个实验中，慢性和急性NTX治疗后皮瓣存活率完全恢复到假手术对照组水平（分别为63.6%±7.6%和61.9%±5.6%，对比55.1%±4.2%和54.9%±4.3%，P<0.05）。慢性胆汁淤积（超过2周）会降低皮瓣存活率，而全身注射NTX可使其恢复。本研究首次提供证据表明，长期升高的阿片能张力会损害皮肤对缺血的耐受性。
