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Objective To investigate the mechanism of Guiqiyiyuan Ointment (GO) for preventing and treating 12C6+ beam radiation induced lung and kidney bystander effect to provide a new strategy for prevention and treatment of clinical radiation injury. Methods Sixty healthy male Wistar rats were randomly and equally divided into 3 groups: NC group, SR group (simple radiation 2ml/kg), GO group(GO 2ml/kg intragastric administration for 7 days). The right side of the lung was modeled by 12C6+beam radiation. After modeling, the rats were killed at 48h. The left lung, left and right kidney tissues were taken from the rats. The DNA methylation rate was detected by ELISA assay, pathological changes were observed by HE staining, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were detected by immunohistochemistry. Results Compared with the NC group, the level of DNA methylation was decreased significantly (P<0.01), the left lung showed inflammation, no abnormal finding was seen in the left and right kidneys, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly increased in the SR group (P<0.01). Compared with the SR group, the level of DNA methylation was increased significantly (P<0.01), the left lung inflammation became better, and the expressions of Dnmt1, Dnmt3a and Dnmt3b were significantly decreased in the GO group (P<0.01). Dnmt1, Dnmt3a and Dnmt3b proteins were expressed in the cytoplasms of bronchial and renal tubular epithelial cells in all the groups. The NC group presented as light brown-brown staining, showing a weak positive expression, the SR group as brown-brown staining, showing astrong positive expression, and the GO group as light brown-brown staining, showing a moderate positive expression. Conclusion The GO can reduce the bystander effect caused by 12C6+ beam radiation, and its mechanism is related to improving the level of DNA methylation.
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Objective To discuss the protective effects ofGuiqi YiyuanOintment on damages caused by heavy ion radiation induced bystander effects; To explore the possible mechanism.Methods Totally 42 Wistar male rats were randomly divided into blank control group, pure radiation group andGuiqi Yiyuan Ointment group. TheGuiqi Yiyuan Ointment group was givenGuiqi Yiyuan Ointment by gavage for two weeks in advance. Later the right lungs of the rats in the pure radiation group andGuiqi Yiyuan Ointment group were radiated once by 2 Gy12C6+, while the blank control group received no radiation. 6, 12, 24 h after radiation all groups of rats were executed. Peripheral hemogram and the levels of IL-6, TGF-β1 and IL-1β in serum of the rats were examined. The changes of lung tissue pathology morphology in the rats were observed by HE staining.Results Compared with the blank control group, the contents of IL-6, TGF-β1 and IL-1β in serum of the pure radiation group increased obviously at 12 h after radiation (P<0.01), and the amount of leukocyte, erythrocyte, blood platelet and hemoglobin distinctly declined at 12 h after radiation (P<0.01); HE staining showed that the alveolar wall was thickened at 24 h after radiation, and there were exudate and inflammatory cell infiltration in the alveolar cavity. Compare with the pure radiation group at 12 h after radiation, the levels of IL-6, TGF-β1 and IL-1β inGuiqi Yiyuan Ointment group decreased significantly at 12 h after radiation (P<0.01). Indexes of blood routine significantly increased (P<0.01), and the pathological changes of lung tissue in rats improved (P<0.01). ConclusionGuiqi Yiyuan Ointment can protect damages caused by heavy ion radiation induced bystander effects.
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Objective To observe the effects of Radix Hedysari on collagen area, hyaluronic acid (HA) and laminin (LN) of lung tissues in rat with pulmonary interstitial fibrosis; To investigate the mechanism and screen the best active ingredients in Radix Hedysari.Methods Totally 144 SPF Wistar rats were randomly divided into control group, model group, metacortandracin group, and Radix Hedysari polysaccharide, flavone and saponin groups were set as high-, medium-, and low-dose groups. Pulmonary interstitial fibrosis models were set up by dropping bleomycin into air tube of rats. All groups were taken corresponding medicine with appropriate dose daily on day 2 after models were established for 28 days. Collagen fibrils in lung tissue were observed by Masson dying and contents of HA and LN in lung tissue of rats in each group were detected by radioimmunoassay.Results Compared with the model group, pulmonary alveoli in Radix Hedysari flavone high-, medium-, and low-dose groups and Radix Hedysari polysaccharide low-dose group were relieved obviously; collagenous fiber area in Radix Hedysari flavone low-dose group, Radix Hedysari polysaccharide medium-dose group, and Radix Hedysari saponin low-dose group decreased obviously. Compared with the model group, the content of HA in Radix Hedysari polysaccharide high-dose group, Radix Hedysari flavone high-, medium-, and low-dose groups, and Radix Hedysari saponin high-dose group decreased obviously; the content of LN in Radix Hedysari polysaccharide high-dose group, Radix Hedysari flavone medium- and low-dose groups, and Radix Hedysari saponin medium- and low-dose groups decreased obviously. Conclusion Polysaccharide, flavone and saponin of Radix Hedysari have the abilities to alleviate inflammation of pulmonary alveoli, inhibit proliferation and deposition of collagen fibrils, and reduce the contents of HA and LA in lung tissue. Among these active ingredients, flavone has the best effect.
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Objective To discuss radix hedysari flavonoids mechanism of preventing pulmonary fibrosis.Methods Totally 216 SPF Wistar rats were randomized into normal group, model group, prednisone group, radix hedysari flavonoids high, medium, and low dose groups, and then pulmonary fibrosis model was established by intratracheal dripping of bleomycin. From the second day after modeling, every treatment group received gavage with the corresponding dose of medicine at the planned time for 7, 14, and 28 continuous days. Expressions of MMP-2 and TIMP-1 protein were detected by immunohistochemical method.Results When radix hedysari flavonoids high dose group was at the 7th, 14th, 28th day, and medium dose group was at the 14th day, MMP-2 protein expression was lower than model group, similar to prednisone group. When radix hedysari flavonoids high dose group was at the 14th, 28th day and medium dose group was at 14th day, TIMP-1 protein expression was lower than model group.Conclusion Radix hedysari flavonoids can adjust the expressions of MMP-2 and TIMP-1 protein at different phases, and tend to make the balance of MMPs/TIMPs, which may be an effective mechanism for the inhibition of fibrosis process.
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Objective To discuss the effects of Radix Hedysari flavonoids on microvessel density (MVD) of pulmonary interstitial fibrosis model rats, and provide evidence for its development. Methods SPF Wistar rats were divided into blank group, model group, prednisone group, and Radix Hedysari flavonoids high-, medium- and low-dosage group. Pulmonary interstitial fibrosis model was established by intratracheal instillation of bleomycin. From the second day after model established, each drug treatment group was administered with corresponding drugs intragastrically at different points in time for 14 and 28 days. MVD was detected by immunohistochemistry. Results Neomicrovessel was increased significantly in pulmonary tissue of model rats of 14 days treatment, but slightly decreased in 28 days. MVD in 14, 28 days model group was significantly more than blank group (P<0.01). MVD in 14, 28 days Radix Hedysari flavonoids high dosage group was significantly less than model group (P<0.01). MVD in Radix Hedysari flavonoids medium-dosage group was between high-and low-dosage group, and MVD in medium-dosage group was similar with that in model group. Conclusion Radix Hedysari flavonoids could inhibit the formation of neomicrovessel in a dose dependent manner.
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Objective To observe the effects of Hedysari flavonoids on TGF-β1 and ultrastructure in lung tissue of rats with pulmonary fibrosis, and explore its mechanism. Methods Wistar rats were randomly divided into blank group, model group, prednisone group and Hedysari flavonoids high-, medium- and low-dose groups. Pulmonary fibrosis model was established by injection of bleomycin via trachea. After 24 h, rats were given drugs by gavage in all treatment groups once daily. The expression of TGF-β1 in lung tissue was detected by immunohistochemistry on d7, d14 and d28, and ultrastructure wasobserved by transmission electron microscope on d28. Results The positive expression of TGF-β1 was found in a few bronchiolar epithelial cell cytoplasm of blank group. Compared with the blank group, the positive expression of TGF-β1 on bronchial epithelial cell significantly increased (P<0.05) on d7, d14, and d28 in model group. Compared with the model group, the positive expression of TGF-β1 were significantly decreased (P<0.05, P<0.01) in Hedysari flavonoids high- and medium-dose groups and prednisone group on d7, d14 and d28. With electron microscopy, collagen fibers within the mediastinum in rat alveolar in model group were significantly increased, cell cytoplasm mitochondria was swollen in type Ⅱ epithelial cell.Mitochondrial crista was broken or disappeared, lamellar bodies significantly reduced. Collagen fibers reduced significantly in all treatment groups, which can improve and change ultrastructure on type Ⅱ epithelial cell. Conclusion Hedysari flavonoids can significantly reduce pathological damage and extracellular matrix deposition of rats with pulmonary fibrosis, which may have connection with inhibiting of TGF-β1 expression.