RESUMEN
ObjectiveThe pulmonary edema （PE） model where the disease was located in the viscera was established according to the treatment principle that patients with the disease location inside should be treated with descending and sinking medicine， combined with changes in the disease tendency， to verify the scientificity of descending and sinking properties of Descurainiae Semen Lepidii Semen （SD）， and to preliminarily elucidate the scientific connotation of descending， ascending， floating and sinking of Chinese medicine. MethodSixty male SD rats were randomly divided into normal control group， model group （20 mg·kg-1）， positive drug group （dexamethasone， 0.075 mg·kg-1） and SD low （1.167 g·kg-1）， medium （2.334 g·kg-1）and high （4.668 g·kg-1） dose groups. The PE model was established by intrapleural injection of 1% carrageenan （2 mL·kg-1）. The evaluation indexes （lung autopsy， amount of pleural effusion， number of white blood cells， lung wet/dry weight ratio， lung water content and lung permeability） were tested to determine the optimal dose of SD decoction for intervention of PE. The relevant indexes of the five major systems （central nervous system， respiratory system， circulatory system， digestive system and urinary system） closely related to the body's Qi movement were detected and changes in the disease tendency in PE rats were analyzed， to determine the descending， ascending， floating and sinking properties of SD. In addition， histopathological changes were investigated by hematoxylin-eosin （HE） staining， and types and numbers of inflammatory cells and mediators were detected to preliminarily explore the mechanism of SD in improving PE. ResultCompared with the conditions in the normal control group， the amount of pleural effusion， number of white blood cells in pleural effusion， lung wet/dry weight ratio， lung water content and lung permeability were increased （P<0.01） in the model group， where the rats presented cough， dyspnea， shortness of breath and arched back， and a small number of them had wet nose and bubble liquid in nostrils. In the autopsy of the rats in the model group， the lungs were enlarged or accompanied by congestion and plenty of pink bubble liquid appeared at the trachea. Compared with the conditions in the model group， SD reduced the amount of pleural effusion， number of white blood cells in pleural effusion， lung coefficient， lung wet/dry weight ratio and lung water content （P<0.01）， and improved pulmonary edema symptoms such as damage， inflammation and infiltration around the lumen， thickening of the trachea， and accumulation of edema fluid， and the SD medium dose group had the best effect on the treatment of PE. In terms of respiratory system， compared with the normal control group， the model group had reduced latent time of cough and asthma （P<0.05， P<0.01） and elevated number of cough and wheezing （P<0.01）. The three SD groups had increased latent time of cough and asthma and decreased number of cough and wheezing （P<0.01）. In terms of urinary system， compared with the normal control group， the model group presented decreased urine volume. The SD low， medium and high dose groups had increased urine volume （P<0.05， P<0.01）， but they had no effect on perspiration. In terms of digestive system， compared with the conditions in the normal control group， the gastric residual rate and gastrin （GT） level were increased （P<0.05， P<0.01）， and the gastric emptying rate and small intestine transit rate were decreased （P<0.01）. The SD low dose group had elevated small intestine transit rate （P<0.01）， and the SD high and medium groups had enhanced gastric emptying rate and small intestine transit rate （P<0.01）， reduced gastric residual rate， lowered GT level to promote gastrointestinal movement and transportation （P<0.01）， and increased motilin （MTL） level to promote gastric emptying in rats （P<0.05， P<0.01）. In terms of circulatory system， compared with the normal control group， the model group displayed reduced left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS） and cardiac output （CO） （P<0.01）， and elevated tendency of heart rate， systolic blood pressure （SBP， P<0.01） and diastolic blood pressure （DBP， P<0.05）. Compared with the model group， the SD low dose group increased LVEF and decreased DBP （P<0.05）， while the SD medium dose group increased LVEF， LVFS， CO and SBP （P<0.01） and decreased DBP （P<0.05）， and the SD high dose group increased LVFS （P<0.01） and decreased SBP （P<0.01） and DBP （P<0.05）. In terms of central nervous system， compared with the conditions in the normal control group， the standing times dropped in the model group （P<0.01）. SD reduced the movement distance， movement time， standing times and activity time in the center of the open field， and increased the rest time and activity time at the edge of the open field （P<0.05， P<0.01）. Moreover， compared with the normal control group， the model group had serious inflammatory infiltration around the lung lumen， thickened trachea with accumulated edema fluid， seriously damaged lung tissue， increased number of white blood cells and percentage of neutrophils in blood （P<0.01）， elevated percentage of monocytes， interleukin-4 （IL-4）， immunoglobulin E （IgE） level and reactive oxygen species （ROS） level in lung tissue （P<0.05，P<0.01）， and decreased IFN-γ in alveolar lavage fluid （P<0.01）. Compared with the model group， SD decreased the number of white blood cells， neutrophil accumulation， pulmonary congestion and interstitial edema， IFN-γ and IL-4 levels in alveolar lavage fluid and ROS level in lung tissue， and increased IgE level （P<0.05， P<0.01）. ConclusionSD had a significant improvement effect on PE model where the disease was located in the viscera. It could regulate the excretion of water by purgation， regulate Qi movement and expel Qi stagnation by descending and sinking lung Qi， and promote purification and descent of lung qi to make Qi movement downward. This indicated SD had the descending and sinking properties. The medium dose of SD decoction exerted the best effect， and its mechanism of action might be through regulating the neutrophil inflammatory response.
RESUMEN
Mahuang Shengmatang was first recorded in the chapter "Reverting Yin Diseases" in the Treatise on Cold Damage （《伤寒论》）. Whether it is a classic prescription created by ZHANG Zhong-jing is controversial among scholars and physicians due to its distinctiveness in contexts and drug composition. In fact， its proven efficacy in a number of clinical cases cannot be denied， and it is rather biased to judge that Mahuang Shengmatang is a fallacy of later generations. The present study pointed out that Mahuang Shengmatang was a representative in the Treatise on Cold Damage in the treatment of diseases with complicated syndromes. In this formula， although the compatibility of drugs effective in dispersion， astringing， nourishing Yin， assisting Yang， clearing heat， dissipating cold， ascending， floating， sinking， and descending seems complex， it follows certain therapeutic principles. Five depression syndromes in the Huangdi Neijing （《黄帝内经》） highly reflect the Five Elements losing the nature， and embody multiple characteristics of the five elements， such as the movement forms， functions， and disease nature. Furthermore， the corresponding treatment methods were pointed out in the Plain Questions · Major Discussion on the Progress of the Six Climatic Changes of Huangdi′s Internal Classic， including "stagnation of wood should be treated by smoothing， stagnation of fire by dispersing， stagnation of earth by attacking， stagnation of metal by dredging， and stagnation of water by inhibiting"， aiming to restore the physiological conditions of the five elements. The indicated syndromes of Mahuang Shengmatang are complex in superior-inferior， asthenia-sthenia， and cold-heat. The five depression syndromes and their treatment methods recorded in the Huangdi's Internal Classic can reflect the key syndrome pathogenesis and therapeutic principles， which are conducive to analyzing the syndrome differentiation and formulating principles of Mahuang Shengmatang. In the disease progression， impaired Yang Qi in greater Yin and inward invasion of cold pathogens in reverting Yin happen in the initial stage of indicated syndromes of Mahuang Shengmatang， with characteristics of water stagnation， earth stagnation， and wood stagnation. Furthermore， mental stagnation and fire stagnation triggered by Yang Qi accumulation in greater Yang and Yang brightness are the secondary consequences. The compatibility of five types of drugs in Mahuang Shengmatang can act on five depression syndromes in a targeted manner. Based on the five-depression theory in the Huangdi′s Internal Classic and available literature， the present study summarized syndrome pathogenesis and medication characteristics of Mahuang Shengmatang， clarified the correlation between formula and syndrome， and reviewed clinical reports in recent years， which is expected to provide references for the clinical application of Mahuang Shengmatang.