- 學位論文
銀杏萃取物對脂多醣體誘導急性肺損傷之影響
Effects of Ginkgo biloba extracts to LPS-induced acute lung injury mice
摘要
急性肺損傷 (acute lung injury, ALI) 為臨床上具有很高盛行率及死亡率的疾病。 其中革蘭氏陰性菌外套膜-脂多醣 (Lipopolysaccharide, LPS) 為引發 ALI 的主要病因之一。本研究探討銀杏葉萃取物 (Ginkgo biloba leaves extract, GbE)保護由LPS 引發的ALI 與其分子機制。先分別以腹腔注射不同劑量的GbE (10、100 和 1000 µg/kg)至小鼠 0.5 小時，再以氣管注射的方式投予100 µg/50µl LPS 。在施予 LPS 後6小時監測動脈血中氣體含量、肺重量、支氣管肺泡灌洗液 (bronchoalveolar lavage fluid, BALF) 及嗜中性白血球的狀況。發現GbE能抑制 LPS 引起動脈血中氧氣含量的降低及二氧化碳的提升。肺病理切片的結果顯示，預處理1000µg/kg GbE能顯著減少LPS引起的病理變化，如出血，組織水腫及嗜中性白血球嗜中性白血球浸潤。進一步分析支氣管肺泡灌洗液及肺組織，發現由LPS增加的嗜中性白血球及提高Myeloperoxidase (MPO) 活性上升會被 GbE (100 和 1000 µg/kg) 所抑制。此外，GbE也會抑制LPS所引發的觸酶 (Catalase, CAT)、超氧化物歧化酶 (superoxide dismutase, SOD) 的活性，和脂質過氧化的程度。接著，GbE也抑制了BALF中，由LPS引發細胞激素的增加，如 Tumor necrosis factor (TNF-α)、Keratinocyte-derived chemokine (KC)、intercellular adhesion molecule-1 (ICAM-1)的表現量。最後，投予 LPS 所引發的mitogen-activated protein kinase (MAPK)、inducible nitric oxide synthase (iNOS)、Cyclooxygenases-2 (COX-2) 和nuclear factor-kappaB (NF-kB) 路徑會被 GbE抑制。所以，GbE可以保護由脂多醣體誘導小鼠急性肺損傷。
並列摘要
Acute lung injury (ALI) in critically ill patients remains the leading cause of mortality and morbidity.Lipopolysaccharide (LPS), a major our membrane component of Gram-negative bacteria, is one of the main risk factors of ALI. To investigate the protective effects of Ginkgo biloba leaves extract (GbE) in LPS-induced ALI and the underlying molecular mechanism.Mice challenged with or without LPS were pretreated with varied doses of GbE for 0.5 h before injection of LPS or saline. ALI was induced by intratracheal injection of LPS (100 µg/50µl). Blood gas in arterial blood, lung edema, and neutrophils sequestration to bronchoalveolar lavage fluid (BALF) fuild were examined 6 h after administration of LPS. Pretreatment with GbE significantly inhibited LPS-induced decrease in oxygen pressure and increase in carbon dioxide in arterial blood.The histopathological study established 1000 µg/kg GbE pretreatment markedly attenuates lung histopathological changes, such as haemorrhaging, interstitial edema, and infiltration of neutrophils into the lung parenchyma and alveolar spaces. Sufficient evidence for GbE (100 and 1000 µg/kg) suppresses activation and infiltration of neutrophils is obtained in BALF cells and myeloperoxidase activity in lung tissue. Furthermore, GbE reduces the activity of catalase (CAT) and superoxide dismutase (SOD), and the level of oxidative damage, and lipid peroxidation, in lung tissue. In addition, the secretion of Tumor necrosis factor (TNF-α), Keratinocyte-derived chemokine (KC), and Intercellular adhesion molecule-1 (ICAM-1) in the BALF after LPS challenge are also inhibted by GbE. Furthermore, mitogen-activated protein kinase (MAPK), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor-kappaB (NF-kB) were activated in 6 h after LPS treatment, which could be blunted by GbE. Therefore,GbE is a potential protective antagonists for LPS-induced ALI in mice.