从“肺虚络痹”探讨大鼠肺纤维化血管新生的防治
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摘要
目的：研究清热化痰法、益气活血法、两法联合运用及两法分阶段运用对博莱霉素诱发肺纤维化大鼠模型的影响，探讨其防治血管新生的理论依据和作用机制。
方法：(1) 理论探讨：在总结络病与肺纤维化血管新生相关性的基础上，探讨“肺虚络痹”的病机及从抗血管新生角度寻求中医药防治肺纤维化的理论依据。(2) 总体实验：①建立大鼠肺纤维化模型；②以呼吸频率、力竭性游泳时间观测大鼠行为学变化；③HE光镜及病理形态学定量分析观察大鼠病理学改变：④天狼星红染色偏光镜下观察肺纤维化大鼠Ⅰ、Ⅲ型胶原的动态变化；⑤链霉亲和素—生物素酶复合物法检测VEGF、ET-1及Ang-2，进行半定量分级分析，并用积分光密度法计算其阳性面积的IOD值；⑥观察肺组织微血管密度改变。(3) 细胞培养：①建立AM、IM细胞模型；②用原位杂交的方法检测TGF-β_1mRNA表达水平；③积分光密度法计算巨噬细胞TGF-β_1mRNA阳性面积的IOD值。
结果：①行为学：两法联合运用治疗28天后，呼吸频率、力竭性游泳时间有明显改善，与模型组比较有显著性差异(P＜0.05)。②病理形态学：模型组7天时病理特点以大量炎性细胞浸润为主，至第28天可见较明显的纤维结缔组织增生，肺组织以胶原沉积、肺纤维化改变为主，肺泡结构破坏或消失，病损范围广泛；两法联合运用治疗28天后，与模型组之间有显著性差异(P＜0.01)。③对Ⅰ、Ⅲ型胶原的影响：模型组早期病变以Ⅲ型胶原为主，Ⅲ／Ⅰ型胶原比例增高，后期病变则以Ⅰ型胶原为主，Ⅲ／Ⅰ型胶原比例下降；两法联合运用组治疗28天后能明显改善在肺间质周围的胶原分型比例，抑制Ⅰ型胶原，保持Ⅲ／Ⅰ型胶原比率。④对相关细胞因子的影响：模型组肺组织中促血管新生因子VEGF、ET-1及Ang-2含量升高，两法联合运用治疗28天后，能降低其高表达水平，VEGF、ET-1及Ang-2分级结果与积分光密
Objective:
To study the effect of Qin Re Hua Tan Principle,Yi Qi Huo Xue Principle, two method associated usages and two method to induct by stages on the model which idiopathic pulmonary fibrosis rat was formed by bleomycin injection via trachea.And explore the academic gist and functional mechanism of preventing and curing the angiogenesis.
Method:
1.The pathogenesis theory of pulmonary asthenia and collaterals arthralgia on angiogenesis of idiopathic pulmonary fibrosis study based on the relativity which have been summarized by the collaterals diseases of TCM and angiogenesis of idiopathic pulmonary fibrosis.
2.Experiment in vivo:①Establishment of the model rats of idiopathic pulmonary fibrosis.②Observation of behavior mistakes on the model rats by measuring the frequency of respiration and the hour of exhaust in swimming.③Survey of pathology remodel according to dyes come from HE in microscope and quantitative analysis.④Espial of the variety on collagen by dyes come from Sirius Red in polarimeter microcope. ⑤Analysis of harf-ration classification data on VEGF ET-1 and Ang-2,account of IOD by the method of integral ray density.⑥The microvessel density changes were observed by SABC.
3.Cell calture:①Establishment of the cell model of Alveolar Macrophage and Intercrop Macrophage.②The cultured cells were stained with nucleic acid hybridization in situ to observe the TGF-β1 mRNA expression.
Results:
①The results showed that there are obvious behavior mistakes in model animals.Compared with the model and two method associated usages group show significant changes(P<0.05).②The changes of morphologic pathology in model group showed that a great deal of phlogistic cells had been soaked in 7th day and hyperplasia of fibrous tissue had been observed in 28th day. Compared with the model and two method associated usages group show significant changes(P < 0.01 ) .③ The proportion of collagen typing arround the interstitial substance was obviously improved on 28th day in two groups as follow : one group which was treated by combined Qin Re Hua Tan Principle and Yi Qi Huo Xue Principle the other is treated by two methods to be conducted by different stages.At the same time ,the type I collagen was inhibited and
方法：(1) 理论探讨：在总结络病与肺纤维化血管新生相关性的基础上，探讨“肺虚络痹”的病机及从抗血管新生角度寻求中医药防治肺纤维化的理论依据。(2) 总体实验：①建立大鼠肺纤维化模型；②以呼吸频率、力竭性游泳时间观测大鼠行为学变化；③HE光镜及病理形态学定量分析观察大鼠病理学改变：④天狼星红染色偏光镜下观察肺纤维化大鼠Ⅰ、Ⅲ型胶原的动态变化；⑤链霉亲和素—生物素酶复合物法检测VEGF、ET-1及Ang-2，进行半定量分级分析，并用积分光密度法计算其阳性面积的IOD值；⑥观察肺组织微血管密度改变。(3) 细胞培养：①建立AM、IM细胞模型；②用原位杂交的方法检测TGF-β_1mRNA表达水平；③积分光密度法计算巨噬细胞TGF-β_1mRNA阳性面积的IOD值。
结果：①行为学：两法联合运用治疗28天后，呼吸频率、力竭性游泳时间有明显改善，与模型组比较有显著性差异(P＜0.05)。②病理形态学：模型组7天时病理特点以大量炎性细胞浸润为主，至第28天可见较明显的纤维结缔组织增生，肺组织以胶原沉积、肺纤维化改变为主，肺泡结构破坏或消失，病损范围广泛；两法联合运用治疗28天后，与模型组之间有显著性差异(P＜0.01)。③对Ⅰ、Ⅲ型胶原的影响：模型组早期病变以Ⅲ型胶原为主，Ⅲ／Ⅰ型胶原比例增高，后期病变则以Ⅰ型胶原为主，Ⅲ／Ⅰ型胶原比例下降；两法联合运用组治疗28天后能明显改善在肺间质周围的胶原分型比例，抑制Ⅰ型胶原，保持Ⅲ／Ⅰ型胶原比率。④对相关细胞因子的影响：模型组肺组织中促血管新生因子VEGF、ET-1及Ang-2含量升高，两法联合运用治疗28天后，能降低其高表达水平，VEGF、ET-1及Ang-2分级结果与积分光密
Objective:
To study the effect of Qin Re Hua Tan Principle,Yi Qi Huo Xue Principle, two method associated usages and two method to induct by stages on the model which idiopathic pulmonary fibrosis rat was formed by bleomycin injection via trachea.And explore the academic gist and functional mechanism of preventing and curing the angiogenesis.
Method:
1.The pathogenesis theory of pulmonary asthenia and collaterals arthralgia on angiogenesis of idiopathic pulmonary fibrosis study based on the relativity which have been summarized by the collaterals diseases of TCM and angiogenesis of idiopathic pulmonary fibrosis.
2.Experiment in vivo:①Establishment of the model rats of idiopathic pulmonary fibrosis.②Observation of behavior mistakes on the model rats by measuring the frequency of respiration and the hour of exhaust in swimming.③Survey of pathology remodel according to dyes come from HE in microscope and quantitative analysis.④Espial of the variety on collagen by dyes come from Sirius Red in polarimeter microcope. ⑤Analysis of harf-ration classification data on VEGF ET-1 and Ang-2,account of IOD by the method of integral ray density.⑥The microvessel density changes were observed by SABC.
3.Cell calture:①Establishment of the cell model of Alveolar Macrophage and Intercrop Macrophage.②The cultured cells were stained with nucleic acid hybridization in situ to observe the TGF-β1 mRNA expression.
Results:
①The results showed that there are obvious behavior mistakes in model animals.Compared with the model and two method associated usages group show significant changes(P<0.05).②The changes of morphologic pathology in model group showed that a great deal of phlogistic cells had been soaked in 7th day and hyperplasia of fibrous tissue had been observed in 28th day. Compared with the model and two method associated usages group show significant changes(P < 0.01 ) .③ The proportion of collagen typing arround the interstitial substance was obviously improved on 28th day in two groups as follow : one group which was treated by combined Qin Re Hua Tan Principle and Yi Qi Huo Xue Principle the other is treated by two methods to be conducted by different stages.At the same time ,the type I collagen was inhibited and
引文
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