| Objective: To research Shabai Moistening Lung particles in the treatment ofradioactive Lung injury on molecular mechanism from TGF-β1/Smads and Wnt/β-catenin signaling pathway, the study will provide new drug targets for clinical treatmentof radioactive Lung injury and the new ways of research.Methods: The radiation-induced lung injury model in rats was established by single x-ray irradiation on2/3of the right lung with20Gy, and let group A blank control group(0Gy+distilled water), B, C, D group was Chinese medicine intervention group (20Gy+Shabai Moistening Lung particles configuring the solution of high, medium and lowdose), E group was administered dexamethasone suspension configuration as thepositive control group, F group was model group (20Gy+distilled water), except thepositive control group that dexamethasone suspension was used by gavage once a dayfor4weeks and subsequent to distilled water till8weeks, the other groups were usedin conjunction with12weeks.Six in each group would be killed2,8,12,16weeks after irradiation，and we takedthe right middle lobe. By HE staining and Masson staining, we observed pathologicalchanges in radiation-induced lung injury clear. By immunohistochemistry and Western-blot, we analyzed expression of signaling protein Smad3, Smad7and β-catenin in rat lung tissue of radiation-induced lung injury. From TGF-β1/Smads signaling pathwayrecognized by the development of radiation-induced lung injury and Wnt/β-cateninsignaling pathway playing the important role in a variety of organ fibrosis, the paperexplored Shabai Moistening Lung particles therapeutic effects in radiation-inducedlung injury.Results:1. HE staining and Masson staining results of the lung tissue in each groupCompared with the control group, model group showed mild-moderate alveolarsepta due to infiltration of inflammatory cells, widened lesions and damaged alveolarstructural; mild fibrosis was bundle, increasing in collagen fibers slightly in the secondweek. On the eighth week, it showed medium-serious alveolitis, expanded lesions anddamaged alveolar structural; It had banded collagen fibers and alveolar structuraldisorder. On the twelfth weeks, it showed severe alveolitis, diffusing a large number ofinflammatory cell infiltration; lots of collagen fibers were a broadband-like, alveolarstructure collapses. The twelfth weeks that inflammatory lesions was reduced, therewas still a large number of collagen fibers hyperplasia, alveolar structure mergetogether.Compared with the model group, Shabai Moistening Lung particles of high,medium and low dose groups were superior to the positive control group, in which thesecond week of high-dose group showed no inflammation and fibrosis; We seen thechanges of mild inflammation on the eighth and twelfth weeks and moderateinflammation on the sixteenth weeks. Except for mild fibrosis visible changes on thetwelfth weeks, there was no significant fibrosis in the other groups. Medium dose groupwas similar to high dose group at each time point and the degree of inflammation fairly;Fibrosis of high dose group was serious on the sixteenth weeks. Low-dose groupshowed mild alveolitis on the second two week, alveolar septa due to inflammatory cellinfiltration widened, lesions confining to the alveolar structure was still intact; it was visible mild fibrosis. On the eighteenth and twelfth weeks, it showed that mild alveolitisand fibrosis, the performance of the sixteenth weeks was severe diffuse alveolarinflammation and moderate fibrosis.2.The expression of Smad3, Smad7and β-catenin in immunohistochemicalanalysis of lung tissueThe expression sites of Smad3and Smad7protein were mainly located incytoplasm and nucleus; The expression of β-catenin focused on the cell membrane andcytoplasm, the nucleus could also be seen in a small amount of expression. Specificperformance:⑴Expression of Smad3protein: Compared with model group, Smad3proteinexpression were decreased in the treatment group (P <0.05); compared with thepositive group, the expression of Smad3protein was decreased in medicine groups (P<0.05), which expression was significantly decreased in high dose group ShabaiMoistening Lung particles.⑵ExpressionofSmad7protein:Comparedwiththemodelgroup,theexpressionof Smad7elevated in Shabai Moistening Lung particles of high and medium dosegroups (P <0.05); Compared with the positive expression group, it increased in highand moderate dose group (P <0.05), and it worked almost the same in both group.⑶Expression of β-catenin protein: Compared with the model group, expressionofβ-catenin protein was decreasedin thetreatment group(P<0.05);Shabai MoisteningLung particles expressing was lower in high-dose group,compared with the positivegroup (P <0.05); compared with the middle dose group, high dose group proteindecreased more significantly (P <0.05).3.The expression of Smad3, Smad7and β-catenin in Western-blot detection onlung tissue: ⑴Expression of Smad3protein: Compared with model group, expression ofShabai Moistening Lung particles was decreased in high and medium dose groups (P<0.05), Smad3protein decreased significantly among high-dose group; Compared withthe medium dose, expression of Smad3protein was significantly decreased in high dosegroup.⑵Expression of Smad7protein: Compared with the model group, the treatmentgroups were significantly higher (P <0.05), and Shabai Moistening Lung particlesplayed an important role in the high dose group; Compared with the model group,protein expression of middle dose group was decreased (P <0.05).⑶Expression of β-catenin protein: Compared with model group, positive groupand low dose group had almost the same protein expression as model group, ShabaiMoistening Lung particles in high and medium dose groups were decreased (P <0.05);compared with the middle dose groups, expression of β-catenin protein wassignificantly decreased in high dose group (P <0.05).Conclusion: Shabai Moistening Lung particles can probably reduce the expression ofSmad3and β-catenin protein, and increase the expression of Smad7. Inflammation inradiation-induced lung injury and the degree of fibrosis can be reduced through jointregulation of the signal pathway of TGF-β1/Smads and Wnt/β-catenin. |
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