Effect of Xuanfei Formula on mTOR / S6K1 signal pathway in acute lung injury induced by lipopolysaccharide in rats
Received:April 17, 2018  
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DOI:10.3969/j. issn. 1005 - 4847. 2018. 04. 004
KeyWord:acute lung injury; Xuanfei formula; p?mTOR; RPS6KB1; rats
                 
AuthorInstitution
余弘吉 上海中医药大学基础医学院经方理论应用研究中心,上海
杨爱东 上海中医药大学基础医学院经方理论应用研究中心,上海
李小茜 上海中医药大学基础医学院经方理论应用研究中心,上海
吴中华 上海中医药大学基础医学院经方理论应用研究中心,上海
符胜光 上海中医药大学基础医学院经方理论应用研究中心,上海
许明亮 上海中医药大学基础医学院经方理论应用研究中心,上海
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Abstract:
      Objective To observe the effect of a Chinese herbs, Xuanfei formula, on mTOR/ S6K1 signaling pathway in rats with acute lung injury induced by endotoxin, and to explore its mechanism. Methods Thirty male Wistar rats were selected and randomly divided into normal control group, model control group, dexamethasone group and XuanfeiActa Lab Anim Sci Sin,August 2018,Vol. 26. No. 4 formula group (high and low dose groups). Lipopolysaccharide (LPS) was injected into the tail vein to prepare rat model of acute lung injury (ALI). The levels of inflammatory factors TNF - α, IL - 1β and IL - 6 in bronchoalveolar lavage fluid (BALF) were detected by ELISA assay. The expression of mTOR protein was detected by immunohistochemistry, p?mTOR protein expression in the lung tissues was measured by western blot, RPS6KB1 gene expression in alveolar lavage fluid was measured by RT?PCR, and the histological changes of rat lung tissues were examined by pathology. Results Compared with the normal group, the TNF - α, IL -1β, IL -6 and RPS6KB1 in the model group were significantly increased ( P <0. 05), and the positive area ratio of mTOR protein and the expression of p?mTOR protein were significantly decreased ( P < 0. 01, P < 0. 05). Compared with the model group, the level of TNF - α, IL - 1β and IL - 6 were significantly decreased ( P < 0. 05) in the dexamethasone group ( P < 0. 05), and the level of TNF - α, IL - 6 and RPS6KB1gene expression were significantly decreased ( P < 0. 01, P < 0. 05), and the positive area ratio of mTOR protein and the expression of p?mTOR protein in the Xuanfei formula groups were significantly increased ( P < 0. 01, P < 0. 05). Pathological examination of the lung tissues of the model group showed local pulmonary hemorrhage and necrosis, dilation of small pulmonary veins, increased number of leucocytes in the blood vessels, pulmonary interstitial edema and inflammatory cell infiltration in the lung tissues. Compared with the model group, the treatment groups showed mild interstitial pneumonia. Conclusions Xuanfei formula has a protective effect on acute lung injury induced by endotoxin in rats. Its mechanism may be related to its downregulation of TNF - α, IL -6, RPS6KB1 gene expression, and upregulation of mTOR and p?mTOR protein expression.
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