大氣微粒於第一型糖尿病大鼠動物模式糖尿病腎病變之研究

Diabetes Nephropathy in Type 1 Diabetes Animal Model Exposed to Ambient Particulate Matter

羅鎧(Kai Lo)

指導教授 ： 鄭尊仁

國立臺灣大學/公共衛生學院/職業醫學與工業衛生研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.01593

摘要

目的：建立糖尿病腎病變動物模式並探討亞慢性暴露週遭大氣微粒對於第
一型糖尿病腎臟之健康效應。

方法：(Sprague-Dawley)SD大鼠注射Streptozotocin(STZ)(55mg/kg body weight)後造成胰島組織受損而無法分泌胰島素，作為第一型糖尿病大鼠動物模式。施打後以血糖高於300mg/dL做為標準，視為誘發成功。使用此糖尿病動物去進行為期16週的亞慢性大氣微粒暴露。每四週採24小時尿液，最後於16週犧牲取其血液、尿液以及器官。

結果：血糖、胰島素以及糖化血色素(HbA1c)等糖尿病相關之生理指標均達到糖尿病標準。此外代表腎功能的白蛋白肌酐酸比值(ACR)在糖尿病組均顯著高於控制組，我們斷定在第一型糖尿病腎病變大鼠動物模式誘導成功。以全身性暴露腔Individual Ventilation Chamber (IVC)做為媒介，使大鼠進行長期大氣微粒全身性呼吸暴露(24hr/day, 7days/week,共16週)，並以呼吸過濾空氣之大鼠做為對照組。結果發現大氣微粒對於糖尿病大鼠在腎功能上-白蛋白肌酐酸比值(ACR)具有負面健康效應(160.86±117.73mg/g vs 267.74±433.17mg/g)，但不具有統計上的顯著效應。但是HbA1c卻發現在暴露組顯著高於控制組，僅觀察到這樣的現象但詳細的機制仍然不明。

結論：雖然大氣微粒並未對糖尿病大鼠在腎病變上具有顯著的負面健康效應，但可稍微觀察到趨勢，此外經過暴露後糖尿病大鼠的HbA1c有顯著上升，然後無血糖資料以及其他資料支持，機制仍然不明，但可做為未來亞慢性大氣微粒暴露於易感族群研究的參考。

關鍵字

第一型糖尿病 ； 腎病變 ； 亞慢性呼吸暴露 ； 腎絲球 ； 大氣微粒

並列摘要

Objective: to establish successful type 1 diabetes nephropathy animals and explore the health effect of ambient particulate matter by this model

Method: male SD rats received 55mg/kg body weight STZ by intravenous injection to induce and become type 1 diabetes. Blood glucose being 300mg/dL is the standard for discriminating it is diabetic or not. And we used this model to deal with 16 weeks subchronic inhalation exposure study.

Results: we observed that insulin and HbA1c reach to the criteria of diabetes mellitus (DM) level and the albumin creatinine ratio(ACR) was significantly higher in DM group than in healthy group. Thus, we consider the type 1 diabetes nephropathy animal model was established successfully. The ambient air particulate matter (PM) was conducted by individual ventilation cage (IVC) system. The whole body inhalation exposure was ongoing (24hr/day, 7days/week and 16 weeks).The diabetes rats in exposed group were compared to non-exposed group and we found that ACR in exposed group was slight higher than non-exposed group but without significant difference(160.86±117.73mg/g vs 267.74±433.17mg/g), but we observed HbA1c was higher in exposed group than in control group. However the detailed mechanism is still unclear.

Conclusions: Our results have shown that ambient air PM has no significant negative health effect but we observe HbA1c is elevated in diabetes exposed rats. Even though the mechanism of increased HbA1c is unclear in exposed group ,we can take this to be the reference in the future study.

並列關鍵字

type 1 diabetes ； Diabetes nephropathy ； subchronic inhalation exposure ； glomerulus ； ambient air particulate matter

參考文獻

Baynes, J. W. (1991). Role of oxidative stress in development of complications in diabetes. Diabetes 40, 405-412.

Bell, R. H. and Hye, R. J. (1983). Animal-models of diabetes-mellitus - physiology and pathology. Journal of Surgical Research 35, 433-460.

Brook, R. D., Franklin, B., Cascio, W., Hong, Y. L., Howard, G., Lipsett, M., Luepker, R., Mittleman, M., Samet, J., Smith, S. C. and Tager, I. (2004). Air pollution and cardiovascular disease - A statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation 109, 2655-2671.

Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813-820.

Chang, C. C., Hwang, J. S., Chan, C. C., Wang, P. Y., Hu, T. H. and Cheng, T. J. (2005). Effects of concentrated ambient particles on heart rate variability in spontaneously hypertensive rats. Journal of Occupational Health 47, 471-480.