大氣微粒對糖尿病大鼠心血管疾病之影響：機轉研究(1/2)

流行病學研究顯示，微粒空氣污染對 心肺疾病的毒性效應是公共衛生上相 當重要的議題，尤其本來及具有心肺 疾病的人更是微粒空氣污染的易感受 性族群。最近的研究顯示，糖尿病患 者可能是另一個微粒空氣污染引發的 心血管疾病有關的易感族群，然而其 毒理機轉並不清楚。本研究以疾病動 物模式，探討微粒空氣污染與糖尿病之間的關係。本研究以strepotozotozocin 誘發之糖 尿病大鼠為疾病動物模式，以在新莊 地區採集之PM2.5 微粒進行氣管灌注 暴露，探討微粒暴露是否會增加糖尿 病大鼠的生理病理變化，包括血漿中 氧化壓力標記8-OHdG 、血管內皮細胞 功能標記VEGF 、NOX 及 Endothelin-1 、發炎前趨細胞激素IL-6 及TNF-α、以及急性反應蛋白 C-reacitve protein ，並比較實驗動物暴 露微粒後肺部發炎情形。 研究結果發現，大鼠於暴露微粒後， 會有顯著的肺部發炎反應，包括肺泡 灌洗液中總細胞數增加、嗜中性球比 例上升，總蛋白質及LDH 活性增加， 但是糖尿病並不會對肺部發炎造成影 響。與健康大鼠相比，糖尿病大鼠血 漿中IL-6 、8-OHdG 、ET-1 顯著增加， NOX 則有顯著的下降。在暴露微粒 後，糖尿病大鼠血漿中的8-OHdG 及 ET-1 皆有顯著上升，NOX 亦有下降的趨勢。本研究發現，微粒空氣污染與糖尿病 同時能造成氧化壓力升高、降低內皮 細胞功能，可能影響發生心血管疾病 的共同途徑，值得進一步研究。Recent epidemiologic studies suggest that the effect of particulate air pollution on the cardiopulmonary system is a significant public health concern. Subjects with existing respiratory and cardiovascular disease are though to be more susceptible to PM exposures. Some researchers suggest that diabetes is another sub-population at risk for PM-associated cardiovascular events. However, the biological mechanism remains unclear. The goal of this study is to use diabetic animal model to examine the relationship between PM exposure and diabetes. We used strepotozotozocin–induced rats as diabetic animal model. Rats were exposed to PM2.5 collected from Hsing-Chung, Taipei by a single intratracheal instillation. The pathophysiological markers were examined after PM exposure, including oxidative stress, endothelial dysfunction, acute phase and proinflammatory cytokine. The pulmonary inflammation and injury were also measured after PM exposure. The results revealed a significant lung inflammation after PM exposure. An increased total cells and proportion of neutrophils, protein and LDH activity in bronchoalveolar lavage were observed in both non-DM and DM rats, however, diabetes did not modify the level of lung inflammation. As compared with non-DM rats, diabetic rats demonstrated significantly higher plasma 8-OHdG, IL-6 and ET-1, and lower nitrate and nitrite. The PM effect was significant in 8-OHdG, ET-1 and nitrite and nitrate in diabetic rats as compared with non-DM. Our study found both PM and diabetes contributed to increased oxidative stress and decreased endothelial function in common pathway. Further studies are needed to clarify the mechanism