在化妝品領域，微米等級的氧化鈦(TiO2)及氧化鋅(ZnO)被很廣泛的應用在物理阻隔UV輻射的防曬產品上，而在這幾年防曬產品為了追求更好的透明度而改用奈米等級的二氧化鈦(TiO2 NP)及奈米氧化鋅(ZnO NP)。研究發現，當皮膚在因為外界因子(紫外線傷害、外傷等)會造成細胞連結(cell junction)疏鬆進而導致奈米物質容易進入皮膚組織而讓細胞吸收。而奈米氧化鋅所造成的細胞毒性和其光催化活性有很大的關係，當奈米氧化鋅顆粒進入皮膚後經光催化形成超氧自由基及氫氧自由基後造成角質細胞氧化壓力上升、DNA損傷等細胞毒性。活性氧物質(reactive oxygen species, ROS)在細胞層面經過多種機制對於細胞胞器造成傷害，特別是粒腺體。ROS造成粒腺體相關的損傷會導致能量生成減少，細胞損傷有關的DAMPs（damage-associated molecular patterns）的累積。當細胞ROS濃度上升而造成粒腺體損傷以及粒腺體損傷後內部的ROS(mtROS)大量釋放，皆會造成NLRP3發炎體的活化，而導致發炎反應，進而促使細胞死亡。過去文獻指出紫檀芪具有相當多的藥理活性，然而紫檀芪調控發炎體活性而抑制發炎機制還未明瞭，其詳細機制及分子機轉還有待研究闡明。本研究目的是探討紫檀芪是否會降低因UVB照射合併奈米氧化鋅所造成的皮膚傷害，並進一步了解紫檀芪是否抑制發炎體活化達到保護作用。
在體外試驗中，利用trypan blue分析HaCaT細胞存活率；並以流式細胞儀及西方墨點法觀察粒腺體功能喪失所導致蛋白質表現量改變、膜電位下降以及mtROS生成等。並以西方墨點法來測定細胞發炎體活化路徑之蛋白表現量，並觀察紫檀芪是透過何種路徑來負調控因UVB照射合併奈米氧化鋅所造成發炎反應。在動物實驗中，使用SKH-1無毛鼠，在照射UVB後處理奈米氧化鋅及不同劑型之紫檀芪，以觀察其急性發炎反應。我們的結果指出紫檀芪可以有效預防UVB照射合併奈米氧化鋅造成皮膚損傷。
在動物實驗中，SKH:HR-1無毛鼠在經由UVB照射150 mJ/cm2誘導皮膚曬傷後暴露2 mg/cm2的奈米氧化鋅，在暴露後24、48、72小時皆可以觀察到經皮水分散失(TEWL)增加及加重皮膚損傷現象，並且在外加紫檀芪的組別可以緩解此現象。而在細胞實驗中發現當人類角質細胞HaCaT cell 同時暴露UVB與奈米氧化鋅後細胞存活率顯著降低，在外加紫檀芪的組別發現存活率顯著的上升。並發現細胞活性氧化物質(Reactive oxidative species, ROS)及粒腺體ROS (mtROS)的上升，在外加紫檀芪的組別發現對於氧化壓力的下降有顯著的效果。西方墨點法的結果證實同時暴露UVB與奈米氧化鋅後會誘發NLRP3發炎體的活化，並引起caspase-1介導之細胞pyroptosis現象，我們的研究結果更進一步的發現細胞暴露奈米氧化鋅會造成細胞內自體吞噬作用失調，形成細胞傷害。而紫檀芪夠緩解上述的現象達到保護效果。綜合上述實驗結果，本研究可以確定UVB照射，合併暴露奈米氧化鋅會加重皮膚損傷，造成上皮細胞氧化壓力上升，導致粒腺體損傷，進而誘導NLRP3發炎體活化及介導細胞pyroptosis。而紫檀芪在作為預防策略下能夠緩解上述的現象，透過降低細胞內部活性氧化物質、緩解粒腺體功能以及自體吞噬作用失調，進一步負調控NLRP3發炎體，並降低細胞pyroptosis現象以達到保護效果。

Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are frequently employed in sunscreens as inorganic physical sun blockers. However, recent studies show when skin cell junction loss the integrity due to environmental risk factor (UV radiation or other Hazard factor ), nanoparticle could easily enter the skin tissue, absorb by skin cell and cause toxicity. ZnONPs are predominantly mediated by formation of superoxide anion radicals and hydroxyl radicals in the presence of light. The free radicals damage organelles, particularly the mitochondria, resulting in energy depletion, accumulation of cytotoxic mediators and cause the NLRP3 inflammasome activation, lead to inflammation, and eventually cause cell pyroptosis. Many studies indicated the anti-inflammatory effects of pterostilbene, but the detail mechanism of anti-inflammatory function is still unclear. The present study is to investigate the inhibition of inflammasome activation by pterostilbene leading to protection of skin damage induced by UVB radiation combined with ZnONPs. In the in vivo study, SKH:HR-1 mice are exposed with ZnONPs on skin after the sunburn induction by 150 mJ/cm2 UVB irradiation. The TEWL degrees is increased and the injury is more severe when combined with ZnONPs. Conversely, the administration of pterostilbene effectively prevents skin damage induced by UVB and ZnONPs. In in vitro study, the cell viability of HaCaT cells is significantly decreased when combined exposure of UVB and ZnONPs. Pterostilbene reverses the decrease of cell viability therefore protects cell survival. Cell oxidative stress and mitochondria ROS are increased when combined exposure of UVB and ZnONPs and eventually leading to NLRP3 inflammasome activation and the caspase-1-depentdent pyroptosis. Administration of pterostilbene diminishes those effects by reducing the ROS production. Accordingly, the skin damage caused by UVB irradiation and ZnONPs is correlated with increased production of oxidative stress, therefore triggered skin inflammation and caspase-1-depentdent pyroptosis. The administration of pterostilbene significantly reduces ROS and oxidative stress therefore attenuates skin damage.

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