Mayhan W G, Sharpe G M
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Microcirculation. 1998;5(2-3):211-8.
The goal of this study was to determine the role of oxygen radicals in impaired histamine-induced increases in venular macromolecular efflux from the hamster cheek pouch. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; MW = 70K) to examine macromolecular extravasation from post-capillary venules in nondiabetic and diabetic (2-4 weeks after injection of streptozotocin) hamsters in response to histamine. Increases in extravasation of macromolecules were quantitated by counting venular leaky sites and by calculating clearance (ml/s x 10(-6)) of FITC-dextran-70K. In nondiabetic hamsters, superfusion with histamine (1.0 and 5.0 microM) increased venular leaky sites from 0 +/- 0 to 17 +/- 6 and 35 +/- 6 per 0.11 cm2, respectively. In addition, clearance of FITC-dextran-70K increased during superfusion with histamine. In contrast, superfusion with histamine did not increase the formation of venular leaky sites (0 +/- 0) or clearance of FITC-dextran-70K in diabetic hamsters. Next, we examined whether alterations in histamine-induced increases in macromolecular efflux in diabetic hamsters may be related to the production of oxygen radicals. We examined whether exogenous application of superoxide dismutase (150 U/ml) could restore impaired histamine-induced increases in macromolecular extravasation in diabetic hamsters. Application of superoxide dismutase did not alter histamine-induced increases in venular leaky sites or clearance of FITC-dextran-70K in nondiabetic hamsters. However, application of superoxide dismutase restored histamine-induced increases in leaky site formation and clearance of FITC-dextran-70K in diabetic hamsters towards that observed in nondiabetic hamsters. These findings suggest that oxygen radical formation appears to contribute to impaired macromolecular efflux in response to histamine during short-term diabetes mellitus.
本研究的目的是确定氧自由基在组胺诱导的仓鼠颊囊小静脉大分子外渗受损中的作用。我们使用活体荧光显微镜和异硫氰酸荧光素葡聚糖（FITC-葡聚糖；分子量=70K）来检测非糖尿病和糖尿病（注射链脲佐菌素后2-4周）仓鼠的毛细血管后小静脉中大分子的渗出情况，以响应组胺。通过计数小静脉渗漏部位和计算FITC-葡聚糖-70K的清除率（ml/s×10(-6)）来定量大分子渗出的增加。在非糖尿病仓鼠中，用组胺（1.0和5.0 microM）灌流分别使每0.11 cm2的小静脉渗漏部位从0±0增加到17±6和35±6。此外，在组胺灌流期间，FITC-葡聚糖-70K的清除率增加。相比之下，用组胺灌流并没有增加糖尿病仓鼠中小静脉渗漏部位的形成（0±0）或FITC-葡聚糖-70K的清除率。接下来，我们研究了糖尿病仓鼠中组胺诱导的大分子外渗增加的改变是否可能与氧自由基的产生有关。我们研究了外源性应用超氧化物歧化酶（150 U/ml）是否能恢复糖尿病仓鼠中受损的组胺诱导的大分子外渗增加。超氧化物歧化酶的应用并没有改变非糖尿病仓鼠中组胺诱导的小静脉渗漏部位的增加或FITC-葡聚糖-70K的清除率。然而，超氧化物歧化酶的应用使糖尿病仓鼠中组胺诱导的渗漏部位形成增加和FITC-葡聚糖-70K的清除率恢复到非糖尿病仓鼠中观察到的水平。这些发现表明，在短期糖尿病期间，氧自由基的形成似乎导致了对组胺反应时大分子外渗受损。
