| 1. ObjectivesThis study used acute lung injury(ALI) model rats as the research object, intervened with the supplementing qi and activating blood circulation herbs astragalus monghol icus (huangqi) and sal via miltiorrhiza (danshen), and valuated of the effect of prevention and treatment, researched the prevention and treatment mechanism of supplementing qi and activating blood circulation herbs astragalus mongholicus (huangqi) and salvia miltiorrhiza (danshen), and explored the traditional Chinese medicine effect targets, investigate the basic pathogenesis of acute lung injury with theory of traditional Chinese medicine, to provide the theoretical foundation for prevention and treatment of ALI by supplementing qi and activating blood circulation method, provide new way for traditional Chinese medicine on treatment of ALI, and expand the scope of the prevention and treatment of diseases of traditional Chinese medicine.2. Methods2.1The establishment and evaluation of ALI rats animal model32male Sprague Dawley rats were randomly divided into model group and normal group. The animal model was induced by intratracheal instillation of LPS (1mg/kg), and was evaluated by lung index, lung permeation index, arterial blood gas analysis, pathological changes.2.2The research of prevention and treatment effect of supplementing qi and activating blood circulation herbs on ALIAstragalus mongholicus (huangqi) and salvia mi miltiorrhiza(danshen) were prepared into low dose(0.125g/ml), medium dose(0.25g/ml), high dose(0.5g/ml), according to1:1proportion.200male Sprague Dawley rats were randomly divided into normal group, model group, herbs low dose group, herbs medium dose group, herbs high dose group, each40. Herbs low dose group, herbs medium dose group, herbs high dose group were gavaged with herbs liquid (0.125g/ml)2ml,(0.25g/ml)2ml,(0.5g/ml)2ml everyday for1week, and then model group, herbs low dose group, herbs medium dose group, herbs high dose group were treated by intratracheal instillation of LPS.5rats were chosen randomly from each group at the1,3,6,12hours after model made, and observed lung permeation index, lung index, arterial blood gas analysis, pathological changes.2.3The research of prevention and treatment mechanism of supplementing qi and activating blood circulation herbs on ALIAstragalus mongholicus and salvia miltiorrhiza were prepared into0.25g/ml according to1:1proportion.60male Sprague Dawley rats were randomly divided into normal group, model group, herbs group, each20. Herbs group were gavaged with herbs liquid2ml everyday for1week, and then model group, herbs group were treated by intratracheal instillation of LPS. At the6hours after model made, haemorheology index and content of NO, H2S, ET-1, CGRP,6-Keto-PGF1α, TXB2in plasm were tested, AQP-1mRNA、AQP-5mRNA、CSEmRNA expression of lung tissue were detected by PCR method, pathological changes were observed also.3. Results3.1The animal model replication was successfulEvaluation results showed that the animal model replication of this study was successful and coinciding the characteristics of ALI animal models, so we can research the prevention and treatment effect and mechanism of the Chinese medicine on ALI further by this animal model.3.2Supplementing qi and activating blood circulation herbs have conspicuous prevention and treatment effect on ALI①Histomorphology:herbs medium dose group, herbs high dose group rats lung tissue structure were clear, alveolar were intact at all time; herbs low dose group alveolar integrity were destroyed at6,12hours; normal group lung t issue structure were clear; model group alveolar integrity were destroyed at3,6,12hours, lots of inflammatory cells infiltration.②Lung injury indicators:normal group, herbs medium dose group, herbs high dose group index of quantitative assessment, lung index, permeation index, PaO2and SaO2were not changed much at each time; model group index of quantitative assessment, lung index, permeation index were higher than normal group, herbs low dose group, herbs medium dose group, herbs high dose group obviously, model group PaO2and SaO2were lower than normal group, herbs low dose group, herbs medium dose group, herbs high dose group obviously (all P<0.05); herbs low dose group index of quantitative assessment, lung index, permeation index were highest at the6hour, higher than normal group, herbs medium dose group, herbs high dose group obviously (all P<0.05), and PaO2and SaO2were lowest at the6,12hours, lower than normal group, herbs medium dose group, herbs high dose group obviously (all P<0.01).3.3The prevention and treatment mechanism of supplementing qi and activating blood circulation herbs on ALI①Haemorheology index:haemorheology index of normal group and herbs group were lower than model group obviously (P<0.01), there were no statistical differences between normal group and herbs group (P>0.05).②Content of NO, H2S, ET-1, CGRP,6-Keto-PGF1α, TXB2in plasm:content of NO, ET-1, TXB2in plasm of herbs group were lower than model group obviously (all P<0.01), content of H2S, CGRP,6-Keto-PGF1α in plasm of herbs group were higher than model group obviously (all P<0.01), there were no statistical differences between normal group and herbs group (P>0.05).③Expression of AQP-1mRNA、AQP-5mRNA、CSEmRNA:expression of AQP-1mRNA、 AQP-5mRNA、CSEmRNA in the lung tissue of herbs group were higher than model group obviously (all P<0.05), there were no statistical differences between normal group and herbs group (P>0.05).4. Conclusion4.1ALI rat animal model replication by intratracheal instillation of LPS was coinciding the characteristics of ALI animal models.4.2The results of pathological changes, index of quantitative assessment, lung index, arterial blood gas analysis, lung permeation index showed that supplementing qi and activating blood circulation herbs have conspicuous prevention and treatment effect on ALI.4.3The prevention and treatment mechanism of supplementing qi and activating blood circulation herbs astragalus mongholicus (huangqi) and salvia miltiorrhiza (danshen) on ALI present in many way, include:①Decreasing the blood viscosity;②Restraining the releasing of endogenous NO and promoting synthesis of endogenous H2S;③Promoting synthesis and releasing of CGRP, restraining the synthesis and releasing of ET-1.④Decreasing TXA2, increasing PGI2, and maintaining the balance of TXA2/PGI2;⑤Promoting the AQP-1mRNA and AQP-5mRNA expression and synthesis in lung tissue, protecting normal fluid metabolism of lung tissue.4.4Qi deficiency and blood stasis is the basic pathogenesis of acute lung injury. Many pathogenesis can cause lung injury, lead to lung failure in governing qi, lung qi deficiency, Zong qi insufficient, abnormal body fluid metabolism, blood movement stagnated, blood stasis, finally formed ALI. Qi deficiency is the fundamental pathogenesis of ALI, and blood stasis is the inevitable result of the further development of illness, therefore, adopt the method of supplementing qi and activating blood circulation depended on pathogenesis of qi deficiency and blood stasis, the supplementing qi and activating blood circulation herbs astragalus mongholicus and salvia miltiorrhiza can effectively prevent and treat ALI. |
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