大氣微粒對心肌受損大鼠之心血管毒性研究

Cardiovascular Toxicity of Ambient Particles in Rats with Myocardial Injury

李偉量(Wei-Liang Li)

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(2008年)

https://doi.org/10.6342/NTU.2008.02556

摘要

流行病學研究指出，大氣微粒會造成心臟衰竭住院率及死亡率的上升。但探討微粒與心臟衰竭相關相關性之毒理研究仍相當有限。因此本研究欲針對心室受損之大鼠暴露在大氣微粒的心臟毒性進行探討。
本研究可概分為兩大部分
第一部分：利用氣管灌注的方式，將注射isoproterenol後產生心肌損傷大鼠，分別在一周及八周後暴露大氣PM2.5微粒、PM10微粒及生理食鹽水之控制組，以心臟超音波觀察其心臟的急性及慢性效應。研究結果未呈現一致性的微粒急性效應；此外，微粒的慢性效應在本研究中也未發現。但由於測量工具及研究設計部分之限制，暴露大氣微粒是否造成心肌受損大鼠心室功能下降之效應及其詳細機轉，仍待未來研究深入探討之。
第二部分：以細粒徑微粒濃縮器進行微粒的長期暴露，利用心肌損傷後大鼠亞慢性暴露大氣濃縮微粒的心臟毒性，並檢視該濃縮微粒系統長期使用之效能及穩定性。將注射isoproterenol後產生心肌損傷大鼠三天後進行全身性呼吸暴露，以吸入大氣濃縮微粒為暴露組，呼吸過濾空氣之實驗動物為對照組，進行為期一個月、每周四天，每天五小時的連續暴露，並分別在暴露前、暴露後兩周及四周後進行尾部靜脈採血測定心肌損傷及心臟衰竭程度。研究結果發現，大氣濃縮微粒暴露會使心臟衰竭功能指標BNP較慢恢復到穩定值，但心肌損傷指標cTnI卻無發現這樣的結論，顯示大氣微粒可能在急性暴露下會有毒性效應，但其詳細作用時間及機轉仍待未來研究進一步探討。

關鍵字

心臟衰竭 ； 心肌損傷 ； 超音波 ； BNP ； Troponin I ； 大氣濃縮微粒 ； 細粒徑微粒濃縮器

並列摘要

Numerous epidemiologic studies have shown that the mortality and hospital admissions of heart failure are associated with ambient particle. However, the toxicological researches on the relationship between ambient particle and heart failure are limited. Thus, we used an animal model of myocardial injury to investigate the cardiovascular toxicity of ambient particle.
Our study are composed of two major parts：
Part Ⅰ：Rats were received 150 mg/kg isoproterenol by subcutaneous injection to induce myocardial injury. Then, rats were exposed to PM2.5、PM10 and saline by intratracheal instillation one and eight weeks after the injection of ISO. The acute and chronic cardiovascular effects were observed using echocardiography. The results showed that acute PM2.5 exposure would lead to decreased LV function, but the similar effects were not observed in PM10. Further, we didn’t observe chronic effect of particles. Because of limitations of echocardiography and study design, the exact relationship between ambient particle and heart failure need further study.
Part Ⅱ：Ultrafine particle concentrator (UFPC) was used to conduct a subchronic exposure in rats administered with 150 mg/kg of isoproterenol by subcutaneous injection. Animals were exposed to concentrated ambient particles (CAPs) for 5-hr/day, 4-day/week for 4-weeks, and controls were exposed to filtered air (FA). BNP for left ventricular function status and cTnI for myocardial injury were measured before exposure, 2 and 4 weeks after exposure. Results of BNP concentration suggest that animals exposed to CAPs may return to normal level later than FA group. As to cTnI, PM didn’t induce further myocardial injury at both CAPs and FA group. Our results suggest that CAPs may cause LV dysfunction shortly after myocardial injury.

並列關鍵字

Heart failure ； Myocardial injury ； Echocardiography ； BNP ； Troponin I ； CAPs ； UFPC

參考文獻

Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, et al. 1996. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med. 335:1342-1350.

Babuin L, Jaffe AS. 2005. Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ. 173:1191-1202

Birmili W, Allen AG, Bary F, Harrison RM. 2006. Trace metal concentrations and water solubility in size-fractionated atmospheric particles and influence of road traffic. Environ Sci Technol. 40:1144-1153.

Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, et al. 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. 109:2655-71.

Burnett RT, Dales R, Krewski D, Vincent R, Dann T, Brook JR. 1995. Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases. Am J Epidemiol. 142:15-22.