| [Background] Acute lung injury (ALI), one of the respiratory system emergency cases, first reported by Ashbaugh in1967, is acute, progressive and hypoxia respiratory failure caused by multiple endo-or ecto-lung etiological factors. ALI has high morbidity and fatality, but its pathogenesis is not fully identified. At present, its genesis and development is regarded as the result of multiple etiological factors. among these, over-imbalance inflammatory reaction is regarded as one of the most important factors. Specific therapy is absent so far.The name "Acute lung injury" was not exist in TCM, but according to clinical manifestation, ALI pertains to "panting patterns","chest bind","panting desertion" and "fulminant panting", of which position of disease is lung and kidney. The vital and pristine pathogenesis is impairment of dispersing and descending function of the lung, disorder of the activities of qi, and also obstruction of poison of lung. The poison factors include heat, toxin, phlegm and stasis, by which the patients'appearance with heat, toxin, phlegm panting, stasis and blocking is significant. To treat these, the method of treatment, including clearing heat and resolving toxin, diffusing the lung and calming panting, sweeping phlegm and opening the orifices, and precipitation, should be used. The results of previous researches revealed that some formula and Chinese pattern medicines directed by either the principle of clearing heat and resolving toxin or clearing heat and transforming phlegm have a certain extent of curative effect.[Objective] To evaluate the curative effect for the phlegm-heat-obstructing-the-lung-type ALI of the management of clearing heat and transforming phlegm, we establish the groups of conventional therapy, conventional therapy adding ulinastatin (UTI) and conventional therapy adding clearing heat and transforming phlegm, and compare them. On the other side, we investigate the mechanism of the management of clearing heat and transforming phlegm according to the animal experiment. In additional, we investigate the dose-effect relationship and safety of Tanreqing injection curing ALI for further study.[Method] We used randomized, single blind methods in clinical research. From February2010to February2012, we collected46patients from the First Affiliated Hospital of Guangzhou TCM University and Guangzhou hospital of TCM, who met the diagnosis criterion of ALI. We randomly divided them into the group of conventional therapy (group A), of conventional therapy adding UTI (group B) and of conventional therapy adding Chinese medicine (group C). The therapeutic regimens of these3groups respectively were conventional therapy, conventional therapy adding UTI and conventional therapy adding clearing heat and transforming phlegm, while their courses of treatment were14days. The patients'symptoms of Chinese medicine and Western medicine, the time of using breathing machine, inflammatory factors in serum and lung injury score (LIS) were observed in the duration of hospital stay.The rat model of ALI was produced with intravenous injecting lipopolysaccharide. After establishing the group of normal control (group A), of ALI model (group B), of UTI (group C), of normal does of Chinese medicine (group D) and of high does of Chinese medicine (group E), we respectively gave them normal sodium5ml, normal sodium5ml, UTI (21, OOOU/kg), Tanreqing(2. lml/kg) and Tanreqing(4.2ml/kg), for3days consecutively, then compared inflammatory factors in the rats'lung homogenate, the wet weight-dry weight ratio(W/D), pathologic change of lung, and the mortality of each group.[Result] The result of clinical study revealed that compared to pretherapy, three groups had significant changes in the aspects of breathing rate, heart rate, saturation of blood oxygen, oxygenation index, sternite and LIS after treatment (P<0.05). Generally speaking, the changes of group B and C were more significant then that of group A, while not obvious between group B and C. According to the viewpoint of Chinese medicine, in group A,3patients were cured,5improved,3not cured,3dead, and total effective rate of this group was57.14%; in group B,7patients were cured,5improved,2not cured,2dead, and total effective rate of this group was68.75%; in group C,7patients were cured,6improved,2not cured,1dead, and total effective rate of this group was75%. But no significant difference was observed. In the aspects of duration of ventilation with breathing machine and the inflammatory factors, such as TNF-α, IL-6and MMP-9, group B and C degraded more significantly than group A(P<0.05), while there was no difference between group B and group C(P>0.05).The result of animal experiment revealed that in the aspect of horizontal comparison of the same day, the indexes, such as TNF-α, IL-6, MMP-9, W/D and pathologic change of lung, of group C, D and E were more significant than those of group B(P<0.05), while no significant difference among group C, D, E(P>0.05). On the other side, in the aspect of longitudinal comparison of the same group, the W/D of C3had more significant decrease than C1,whle significant decrease of TNF-α was present between C2and Cl, D2and D1, E3and El(P<0.05), but no such change of IL-6or MMP-9. During these3days, different extent of improve in W/D and pathologic change of lung was observed day by day. A rat of group B died in the first day, one of group C died in the third day, one of group D died in the second day, while a rat of group E died in everyday. The mortality of group B, C and D was5.6%, while group E was16.7%. Besides, half rats of group E appeared frequent and loose stool.[Conclusion]1. Conventional therapy, conventional therapy adding UTI and conventional therapy adding the management of clearing heat and transforming phlegm are effective for ALI, reflected in the improve of the patients'clinical performance, imageology examination and laboratory examination. The latter two are better than conventional therapy, for the time of using breathing machine was shorter and inflammatory factors in serum were less, while they had no significant difference with each other. One of the mechanisms of the management of clearing heat and transforming phlegm curing the phlegm-heat-obstructing-the-lung-type ALI is decrease the content of TNF-α, IL-6, MMP-9in serum. It can improve the phlegm-heat-obstructing-the-lung-type ALI, arrest its growth to ARDS, shorten the time of using breathing machine and enhance curative effect.2. According to the viewpoint of Chinese medicine, conventional therapy adding the management of clearing heat and transforming phlegm has some curative effect for the phlegm-heat-obstructing-the-lung-type ALI, but shows no significant difference with conventional therapy or conventional therapy adding UTI, thus the research of larger sample size is required. In additional, we find the patiens'stool of conventional therapy adding clearing heat and transforming phlegm is soft, or even sloppy. Basis on the theory of "lung and large intestine are exterior and interior", purgation helping downbear lung-qi and clear lung-heat, it is regarded as one of the mechanisms of the management of clearing heat and transforming phlegm. Therefore, it can enhance curative effect by adding the herb for relieving constipation by purgation on the base of the pattern identification and using he management of clearing heat and transforming phlegm.3. UTI, normal does of Tanreqing and high does of Tanreqing has respectively some curative effect for ALI rats, which has no significant difference with each other. The mechanism is that the content of inflammatory factors such as TNF-a, IL-6and MMP-9in lung is decreased so that the inflammatory reaction is gentler, pathologic change of lung is improved and therefore lung is protected.4. In the second day and the third day, the content of TNF-α in the rats'lung homogenate from the group of UTI, normal does of Tanreqing and high does of Tanreqing was lower than in the first day. TNF-α displays the trend of day-by-day decrease, possibly concerned with that it is the one of the pro-inflammatory factors and the earliest and the most important endogenous transmitter in the inflammatory reaction.5. When successive administration to the second day and the third day, rats'W/D and pathologic change of lung improved compared to the first day, which reveals that the effect of successive administration is better than administration only one time.6. Compared with the normal does of Tanreqing, high does fails to benefit the ALI rats, instead, makes the incidence of adverse effect and the mortality of this group seem higher.
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