肺吸入绿原酸β-环糊精包合物治疗急性肺损伤

Pulmonary delivery of chlorogenic acid β-cyclodextrin inclusion complexes for therapy of acute lung injury

目的制备适于肺吸入给药的绿原酸β-环糊精包合物(CGA-β-CD),评价其对急性肺损伤(ALI)的疗效。方法用研磨法制备了CGA-β-CD,红外光谱法验证包合物结构。采用过氧化氢(H_2O_2)经气管喷入建立ALI大鼠模型后,动物分为4组:模型组、CGA-β-CD肺部给药组、CGA肺部给药组和地塞米松肺部给药组。HE染色观察肺组织病理变化,ELISA法检测肺泡灌洗液中的TNF-α和IL-1β含量,检测肺组织中还原型谷胱甘肽(GSH)及丙二醛(MDA)含量。结果肺组织病理学显示,CGA-β-CD与CGA对H_2O_2诱导的ALI有明显治疗作用;与模型组相比,CGA-β-CD组肺泡灌洗液中TNF-α和IL-1β明显降低(P<0.05),肺组织中MDA水平明显降低(P<0.01),GSH水平明显升高(P<0.01)。结论 CGA-β-CD适于肺吸入给药,并能通过抑制炎症因子、减轻氧化损伤等作用减轻大鼠ALI。CGA-β-CD有望成为有效治疗ALI的肺吸入制剂。

Objective Chlorogenic acidβ-cyclodextrin inclusion complexes(CGA-β-CD)suitable for pulmonary delivery was prepared and evaluated for its effect on acute lung injury(ALI).Methods CGA-β-CD was prepared by the grinding method,and the formation of CGA-β-CD was verified by the infrared spectroscopy.After the rat model of ALI was established by intratracheal injection of hydrogen peroxide(H2O2),the rats were divided into 4 groups:the model group,CGA-β-CD lung delivery group,CGA lung delivery group,and dexamethasone lung delivery group.HE staining was used to examine the pathological changes in lung tissues.The content of TNF-αand IL-1βin alveolar lavage fluids was detected by ELISA.The content of reduced glutathione(GSH)and malondialdehyde(MDA)was detected in the lung tissues.Results The histopathologc examination showed that CGA-β-CD and CGA had significant therapeutic effect on the H2O2-induced ALI.Compared with the model group,the contents of TNF-αand IL-1βin the alveolar lavage fluid were significantly decreased in the CGA-β-CD group(P<0.05).In the lung tissue,the level of MDA was significantly reduced(P<0.01),while the level of GSH was significantly increased(P<0.01),all in the CGA-β-CD than in the model group.Conclusion CGA-β-CD was suitable for the pulmonary delivery administration,which could alleviate ALI in rats by inhibiting inflammatory factors and reducing oxidative damage.CGA-β-CD is expected to be a pulmonary delivery preparation for the effective treatment of ALI.