OBJECTIVE： To observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine （TCM）, on the janus kinase （JAK）/signal transducer and activator of transcription （STAT） pathway and matrix metalloproteinases ...OBJECTIVE： To observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine （TCM）, on the janus kinase （JAK）/signal transducer and activator of transcription （STAT） pathway and matrix metalloproteinases （MMPs） in a chronic obstructive pulmonary disease （COPD） rat model with lung deficiency in terms of TCM＇s pattern differentiation. METHODS： Rats were randomly divided into a normal group, model group, Liuweibuqi group, Jinshuibao group, and spleen aminopeptidase group （n= 10）. Aside from the normal group, all rats were ex-posed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model with lung deficiency. Models were established after 28 days and then the normal and model groups were given normal saline （0.09 g/kg）, Liuweibuqi group was given Liuweibuqi capsule （0.35 g/kg）, Jinshuibao group was given Jinshuibao capsules （0.495 g/kg）, and the spleen group was given spleen aminopeptidase （0.33 mg/kg）, once a day for 30 days. Changes in symptoms, signs, and lung histology were observed. Lung function was measured with a spirometer. Serum cytokines were detected using enzyme-linked immunosorbent assay, and changes in the JAK/STAT pathway, MMP-9, and MMPs inhibitor 1 （TIMP1） were detected by immunohistochemistry, RT-PCR, and western blotting, respectively.RESULTS： Compared with the normal group, lung tissue was damaged, and lung function was reduced in the model control group. Additionally, the levels of interleukin （IL）-1β, y interferon （IFN-γ）, and IL-6 were higher, while IL-4 and IL-10 were lower in the model control group than those in the normal group. The expressions of JAK1, STAT3, ρ-STAT3, and MMP-9 mRNA and protein in lung tissue were higher, and TIMP1 mRNA and protein was lower in the model group compared with the normal group. After treatment, compared with the model group, the expression of inflammatory cytokines was lower in each treatment group, and expressions of JAK/ STAT pathway, MMPs were lower. Compared with the positive control groups, the Jinshuibao and spleen aminopeptidase groups, lung function was better, and JAK1, STAT3, and p-STAT3 protein were lower and TIMP1 was higher in the Liuweibuqi group.CONCLUSION： Liuweibuqi capsules can improve the symptoms of COPD possibly by regulating the expression of the JAK1/STAT3 pathway and MMP9/ TIMP1.展开更多
目的探讨六味补气胶囊对COPD模型大鼠JAK/STAT通路及炎性反应的影响及相关的分子机制。方法体外构建大鼠COPD模型,45只大鼠随机分为3组,对照组,模型组和实验组,每组15只。对照组只灌胃处理等量0.9%氯化钠溶液。模型组利用香烟暴露法制...目的探讨六味补气胶囊对COPD模型大鼠JAK/STAT通路及炎性反应的影响及相关的分子机制。方法体外构建大鼠COPD模型,45只大鼠随机分为3组,对照组,模型组和实验组,每组15只。对照组只灌胃处理等量0.9%氯化钠溶液。模型组利用香烟暴露法制作大鼠COPD模型,灌胃处理等量0.9%氯化钠溶液。实验组在造模成功后采用六味补气胶囊对COPD模型大鼠进行灌胃治疗2周。利用Western blot法检测JAK2/p-JAK2和STAT3/pSTAT3的蛋白表达,利用ELISA法检测炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6和干扰素γ(IFN-γ)水平,以及化学定量法检测基质金属蛋白酶(MMP)-9、MMP-12水平。结果 Western blot结果显示,与对照组比较,模型组大鼠JAK2/p-JAK2和STAT3/p-STAT3的蛋白表达显著提高,与模型组比较,六味补气胶囊显著抑制COPD模型大鼠JAK2/p-JAK2和STAT3/p-STAT3的蛋白表达(P<0.05);ELISA结果显示,与对照组比较,模型组大鼠TNF-α、IL-1β、IL-6以及IFN-γ水平显著提高,六味补气胶囊显著下调COPD模型大鼠TNF-α、IL-1β、IL-6以及IFN-γ水平(P<0.05);化学定量法检测结果显示,与对照组比较,模型大鼠MMP-9、MMP-12水平显著提高,而六味补气胶囊显著下调COPD模型大鼠MMP-9、MMP-12水平(P<0.05)。结论六味补气胶囊能显著抑制COPD大鼠炎症反应,其分子机制可能与抑制JAK/STAT通路相关。展开更多
基金Supported by The National Natural Science Foundation Project:Study on the Metabolism of Chronic Obstructive Pulmonary Disease Pulmonary Qi Deficiency Syndrome and Cerebral Cortex Correlation Spectrum(No.81072781)
文摘OBJECTIVE： To observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine （TCM）, on the janus kinase （JAK）/signal transducer and activator of transcription （STAT） pathway and matrix metalloproteinases （MMPs） in a chronic obstructive pulmonary disease （COPD） rat model with lung deficiency in terms of TCM＇s pattern differentiation. METHODS： Rats were randomly divided into a normal group, model group, Liuweibuqi group, Jinshuibao group, and spleen aminopeptidase group （n= 10）. Aside from the normal group, all rats were ex-posed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model with lung deficiency. Models were established after 28 days and then the normal and model groups were given normal saline （0.09 g/kg）, Liuweibuqi group was given Liuweibuqi capsule （0.35 g/kg）, Jinshuibao group was given Jinshuibao capsules （0.495 g/kg）, and the spleen group was given spleen aminopeptidase （0.33 mg/kg）, once a day for 30 days. Changes in symptoms, signs, and lung histology were observed. Lung function was measured with a spirometer. Serum cytokines were detected using enzyme-linked immunosorbent assay, and changes in the JAK/STAT pathway, MMP-9, and MMPs inhibitor 1 （TIMP1） were detected by immunohistochemistry, RT-PCR, and western blotting, respectively.RESULTS： Compared with the normal group, lung tissue was damaged, and lung function was reduced in the model control group. Additionally, the levels of interleukin （IL）-1β, y interferon （IFN-γ）, and IL-6 were higher, while IL-4 and IL-10 were lower in the model control group than those in the normal group. The expressions of JAK1, STAT3, ρ-STAT3, and MMP-9 mRNA and protein in lung tissue were higher, and TIMP1 mRNA and protein was lower in the model group compared with the normal group. After treatment, compared with the model group, the expression of inflammatory cytokines was lower in each treatment group, and expressions of JAK/ STAT pathway, MMPs were lower. Compared with the positive control groups, the Jinshuibao and spleen aminopeptidase groups, lung function was better, and JAK1, STAT3, and p-STAT3 protein were lower and TIMP1 was higher in the Liuweibuqi group.CONCLUSION： Liuweibuqi capsules can improve the symptoms of COPD possibly by regulating the expression of the JAK1/STAT3 pathway and MMP9/ TIMP1.
文摘目的探讨六味补气胶囊对COPD模型大鼠JAK/STAT通路及炎性反应的影响及相关的分子机制。方法体外构建大鼠COPD模型,45只大鼠随机分为3组,对照组,模型组和实验组,每组15只。对照组只灌胃处理等量0.9%氯化钠溶液。模型组利用香烟暴露法制作大鼠COPD模型,灌胃处理等量0.9%氯化钠溶液。实验组在造模成功后采用六味补气胶囊对COPD模型大鼠进行灌胃治疗2周。利用Western blot法检测JAK2/p-JAK2和STAT3/pSTAT3的蛋白表达,利用ELISA法检测炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6和干扰素γ(IFN-γ)水平,以及化学定量法检测基质金属蛋白酶(MMP)-9、MMP-12水平。结果 Western blot结果显示,与对照组比较,模型组大鼠JAK2/p-JAK2和STAT3/p-STAT3的蛋白表达显著提高,与模型组比较,六味补气胶囊显著抑制COPD模型大鼠JAK2/p-JAK2和STAT3/p-STAT3的蛋白表达(P<0.05);ELISA结果显示,与对照组比较,模型组大鼠TNF-α、IL-1β、IL-6以及IFN-γ水平显著提高,六味补气胶囊显著下调COPD模型大鼠TNF-α、IL-1β、IL-6以及IFN-γ水平(P<0.05);化学定量法检测结果显示,与对照组比较,模型大鼠MMP-9、MMP-12水平显著提高,而六味补气胶囊显著下调COPD模型大鼠MMP-9、MMP-12水平(P<0.05)。结论六味补气胶囊能显著抑制COPD大鼠炎症反应,其分子机制可能与抑制JAK/STAT通路相关。
