電子煙氣膠對動脈硬化的影響：粒徑分佈和化學成分的作用

Effects of Electronic Cigarette Aerosols on Atherosclerosis: Role of Particle Size Distribution and Chemical Compositions

陳彩鈴(Tsai-Ling Chen)

指導教授 ： 蕭大智

國立臺灣大學/工學院/環境工程學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202103006

摘要

近年來市面上流行一種新興菸品電子煙，其原理是將金屬加熱芯通電產生熱能，加熱電子煙油產生煙霧。由於非透過燃燒方式，使用者認為其比傳統煙草香菸健康。然而，含有甘油、丙二醇及人工香精的電子煙油成分會在加熱過程中分解，產生有害副產物並被使用者吸入。此外，電子煙的加熱芯是由金屬零件所構成，已被證實其金屬成分會隨著霧化過程排放。這些有毒物質在人體呼吸道中的沉積會受到粒徑分佈的影響。因此，為了識別傳統香煙和電子煙的健康危害差別，本研究分析了這兩種菸品煙霧的物化特性，包含粒徑分佈、金屬及多環芳烴 (PAHs) 成分，並利用多途徑粒徑沉積模式 (MPPD) 模擬出顆粒沉積於人體呼吸道機率及區域，應用於增量終身致癌風險 (ELCR) 來評估兩種煙品的致癌風險。另一方面，由於吸入傳統煙草煙霧已被證實會造成動脈硬化發展，本研究利用人體主動脈內皮細胞 (HAECs) 及 ApoE-/- 小鼠暴露實驗，來觀察電子煙對動脈硬化的影響。
化學成分結果顯示，電子煙煙霧中的金屬鉻、錳、鎳、釩，以及香菸煙霧中的鎘、錳、鎳皆超過美國毒性物質及疾病登記署 (ATSDR) 規範的吸入最低風險值 (MRL)。由於電子煙是透過加熱方式霧化煙油並非燃燒，因此其產生的多環芳烴量遠低於香煙。氣膠物理特性結果顯示，電子煙與香菸產生的總顆粒濃度都為107 #/cm3。顆粒吸入人體後，兩者皆以沉積在肺泡區域為主，基於質量的總沉積機率電子煙為18.60%，香菸為15.44%。根據化學成分及肺部沉積劑量結果，電子煙的增量終身致癌風險值低於香煙。
細胞實驗方面，HAECs 暴露於電子煙油24小時後，觀察到活性氧物質 (ROS) 量顯著上升，mRNA 表達結果其差異與控制組相比皆未達到統計意義，但有觀察到劑量依賴性的現象。因此推測煙油中的成分可能會使內皮細胞功能受損並引起發炎反應。然而，在氣膠萃取物暴露組沒有觀察到清楚的效應，推測與用濾紙收集氣膠方式有關。濾紙收集為顆粒物質而非氣相污染物，此外，收集到的顆粒可能因其揮發性而損失。動物暴露結果方面，ApoE-/- 小鼠經短期及高劑量電子煙暴露後，頸動脈斑塊面積比例及內皮mRNA表達量與非暴露組相比皆未達到統計意義。

關鍵字

電子煙 ； 多途徑粒徑沉積模式 ； 增量終身致癌風險 ； 動脈硬化

並列摘要

A new type of cigarette product, electronic cigarettes (ECs), has become popular in recent years. ECs work by energizing the metal heating element to generate heat and evaporating the e-liquid to produce vapor. Due to the non-combustion process, users believe that it is healthier than traditional tobacco cigarettes (TCs). However, e-liquid ingredients containing vegetable glycerin, propylene glycol, and artificial flavoring will undergo thermal decomposition and produce harmful by-products inhaled by users. In addition, the heating element of EC is mainly composed of metals that have been confirmed can be transferred into aerosol during vaporization. The deposition of these toxic substances in the human respiratory tract will be affected by the particle size distribution. Therefore, to identify the difference in health hazards between TCs and ECs, this study analyzes both cigarette aerosols' physical and chemical properties, including particle size distribution, metals, and polycyclic aromatic hydrocarbons (PAHs). The multiple-path particle dosimetry model (MPPD) is used to simulate the probability and area of particles deposited in the human respiratory tract and finally applies to excess lifetime cancer risk (ELCR) to assess the cancer risk of these two cigarette products. Since inhalation of TC smoke has been proven to cause the development of atherosclerosis, human aortic endothelial cells (HAECs) and ApoE-/- mice were used in this study to investigate the effects of inhaling EC aerosols on atherosclerosis.
For chemical composition analysis, Cr, Mn, Ni, V in EC vapor, and Cd, Mn, Ni in TC smoke exceed the inhalation minimum risk level (MRL) announced by the U.S. Agency for Toxic Substances and Disease Registry (ATSDR). Since EC produces vapor by evaporation rather than combustion, polycyclic aromatic hydrocarbon levels in EC vapor are much lower than TC smoke. The physical properties of aerosols show that the total particle concentration of EC and TC aerosols is up to 107 #/cm3. Both particles mainly deposit in the alveolar region after inhalation, and the total mass-based deposition fraction is 18.60% for EC and 15.44% for TC. Based on the chemical composition and lung deposited doses, EC aerosol has a lower ELCR value than TC aerosol.
For HAECs results, reactive oxygen species (ROS) levels increased significantly after direct exposure to e-liquid. The results of mRNA expression are not statistically significant compared with the control group but exhibit a dose-dependent phenomenon. Therefore, it is considered that the ingredients in the e-liquid have the potential to impair endothelial cell function and cause an inflammatory response. However, no clear effects were observed in the aerosol extract treatment, which may be due to the filter sampling method. The filter collected aerosols while not the gas-phase pollutants. Moreover, the collected aerosols may be changed due to their volatility. Furthermore, for ApoE-/- mice exposure study, the difference of plaque accumulation and the mRNA expression in the carotid artery between the vaping group and the non-vaping group did not reach statistical significance.

並列關鍵字

E-cigarette ； MPPD ； ELCR ； Atherosclerosis

參考文獻

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