2011-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649531摘要：流行病學研究顯示，微粒空氣污染與心肺疾病的罹病率或死亡率有關，特別是患有有心肺相關疾病的個人更容易受到微粒空氣污染的影響，糖尿病患者也是微粒空氣污染心血管疾病的易感族群，然而生物機轉並不清楚。研究發現微粒與糖尿病對心血管危險因子具交互作用，且會增加胰島素阻抗，顯示微粒空氣污染對糖尿病大小血管併發症的發生及進展有其效應。我們最近的研究更發現，在大血管尚未產生明顯病變之前，微粒就已經造成第二型糖尿病大鼠腎臟病理的變化。糖尿病腎病變是造成末期腎病需接受腎臟透析治療的最大原因，台灣也因洗腎造成相當大的健保負擔，所以探討微粒空氣汙染對糖尿病腎病變的效應，有重大意義。本研究將探討交通及工業汙染地區，(亞)慢性微粒暴露，對第一、二型糖尿病大鼠糖尿病腎病變之效應。第一、二年計畫將以第一、二型糖尿病大鼠動物模式，使用本實驗室開發之微粒暴露系統(IVC exposure system)進行亞慢性及慢性暴露，測量尿中之白蛋白排泄以及尿中白蛋白-肌酐酸比值；腎絲球傷害早期指標Smad1，Collagen IV及腎小管傷害指標beta2-microglobulin；此外將觀察病理學上的變化，包括光學顯微鏡(H&E，PAS)，免疫染色(Smad1，collagen IV，IL-6，TGF-beta，CD68，MMP-9)，以及電子顯微鏡檢查，我們也將測量血中之Renin，TGF-beta與IL-6，配合暴露監測資料，嘗試回答機轉。第三年將延續前兩年的研究，除第一、二年所在之交通汙染地區外，於工業汙染地區進行研究，結果可與前二年結果進行整合比較，以瞭解不同微粒汙染對糖尿病腎病變之效應。本研究結果將可增進微粒空氣污染與糖尿病及其血管併發症相關生物機轉瞭解，結果也可應用於風險評估，對於預防微粒相關疾病及法規制訂將有所助益。<br> Abstract: Epidemiological studies have shown an association between particulate air pollution and cardiopulmonary mortality and morbidity, particularly in susceptible population. Recent studies suggest that diabetes mellitus (DM) is sub-population at risk for particular matter (PM)-associated cardiovascular disease (CVD). However, the biological mechanism remains unclear. Recent studies showed that PM may impair glucose tolerance and increase insulin resistance (IR) resulting in diabetic macro- and microvascular complication in diabetic animal models. Our findings showed PM effects on kidney pathology, including glomerulosclerosis and tubular damage before macrovascular change. These observations indicate that PM may affect the diabetic nephropathy (DN). DN is the major cause leading to end-stage renal disease (ESRD) and renal replacement therapy. Given the public health implications of PM-related CVD in diabetes, it is important to elucidate the relationship between PM and DN and their underlying mechanisms. The goal of this study is to use type 1 and type2 DM animal model to investigate whether sub-chronic and chronic inhalation exposure to ambient PM exacerbate the onset, early phase progression and progression to proteinuria of DN. DM rats will be exposed to ambient PM via novel design IVC exposure system. Early phase urinary markers of DN (Smad1, collagen IV, beta 2 microglobulin), urinary albumin excretion, and urinary albumin-creatinine ratio (UACR) will be examined. In addition, kidney pathology with special (H&E, PAS) and immunostaining (Smad1, collagen IV, IL-6, TGF-beta, CD68, MMP-9) using light microscopy and electron microscopy will be studied. In the 1st and 2nd year, we are planning to examine the sub-chronic and chronic effects (23hr/day, 7 days/week, for 12 and 24 weeks) of PM exposure in STZ-induced type 1 DM rats and high-fat-diet-STZ induced type 2 DM rats using IVC exposure system in urban traffic area. In the 3rd year, we are planning to compare the effect of PM in industrial area on DN. Our results will help us better understand the PM toxicity in DN. The results will also be used for risk assessment and regulatory setting.