Using the latest reported homologous Chemokine receptors （PDB ID： 3ODU, 3OE0 and 3OE6） as templates, twenty models of angiotensin II （Ang II） type 1 （AT1） receptor （known as p30556） were generated by multiple...Using the latest reported homologous Chemokine receptors （PDB ID： 3ODU, 3OE0 and 3OE6） as templates, twenty models of angiotensin II （Ang II） type 1 （AT1） receptor （known as p30556） were generated by multiple templates homology modeling. According to the results of the initial validation of these twenty models, the model 0020 was finally chosen as the best one for further studies. Then, a 2 ns molecular dynamic （MD） simulation for model 0020 was conducted in normal saline （0.9%, w/F） under periodical boundary conditions, which was followed by docking studies of model 0020 with several existing AT1 receptor blockers （ARBs）. The docking results reveal that model 0020 possesses good affinities with these docked ARBs which are in accordance with both the IC50 inhibitor values and their curative effects. The results also show more potent interactions between the model 0020 and its ARBs than those of ever reported results, such as hydrogen bonds, hydrophobic interactions, and especially cation-n interactions and π-π interactions which have never been reported before. This may reveal that the structure of the model 0020 is quite close to its real crystal structure and the model 0020 may have the potential to be used for structure based drug design：展开更多
Objective： To observe the effect of moxibustion therapy on heme oxygenase-1（HO-1） and monocyte chemoattractant protein-3（MCP-3） protein expressions in the colonic mucosa of rats with Crohn＇s disease（CD）, and t...Objective： To observe the effect of moxibustion therapy on heme oxygenase-1（HO-1） and monocyte chemoattractant protein-3（MCP-3） protein expressions in the colonic mucosa of rats with Crohn＇s disease（CD）, and to explore the intestinal mucosal immune mechanism of moxibustion therapy in treating CD. Methods： The CD rat model was established using the internationally accepted Morris method. The rats were randomly divided into a model group, a herbal cake-partitioned moxibustion group, a mild moxibustion group, a cigarette moxibustion group and a hot compress group, which were compared with the normal group. Except the normal group and the model group, rats in the other groups accepted different moxibustion therapies on bilateral Tianshu（ST 25）. Hematoxylin-eosin（HE） staining was conducted and the pathological changes of the colon were observed under light microscope; the expressions of HO-1 and MCP-3 protein in rat＇s colonic mucosa were determined by immunohisto-chemistry. Results： Compared with the normal group, rats in the model group showed mucosal defect, villus destruction or loss, submucosal congestion and edema, glandular destruction or disappearance, reduced goblet cells, ulcer formation, significantly increased positive target area and positive target integral optical density of HO-1 and MCP-3 protein expression（all P〈0.01）. After treatment, compared with the model group, colonic mucosa was significantly improved in the herbal cake-partitioned moxibustion group and the mild moxibustion group, which mainly showed that the intestinal glands were arranged regularly, ulcer surfaces were covered by the neoformative epitheliums, or intestinal ulcers were replaced by the nascent granulation tissue, and submucosal edema was alleviated, with a small amount of inflammatory cell infiltration. The total areas and the integral optical densities of the positive targets for rat＇s colonic mucosa HO-1 and MCP-3 protein expressions were decreased（all P〈0.01）. Compared with the cigarette moxibustion group and the hot compress group, the total areas and the integral optical densities of the positive targets for rat＇s colonic mucosa HO-1 and MCP-3 protein expressions were significantly decreased（all P〈0.01） in the herbal cake-partitioned moxibustion group and the mild moxibustion group. Conclusion： Herbal cake-partitioned moxibustion and mild moxibustion can significantly improve the inflammatory response of colonic mucosa in CD rats. It can down-regulate the expressions of HO-1 and MCP-3 proteins in the colonic mucosa of CD rats, which may be one of the mechanism in intestinal mucosal immunity caused by moxibustion therapy.展开更多
基金Project(20876180)supported by the National Natural Science Foundation of China
文摘Using the latest reported homologous Chemokine receptors （PDB ID： 3ODU, 3OE0 and 3OE6） as templates, twenty models of angiotensin II （Ang II） type 1 （AT1） receptor （known as p30556） were generated by multiple templates homology modeling. According to the results of the initial validation of these twenty models, the model 0020 was finally chosen as the best one for further studies. Then, a 2 ns molecular dynamic （MD） simulation for model 0020 was conducted in normal saline （0.9%, w/F） under periodical boundary conditions, which was followed by docking studies of model 0020 with several existing AT1 receptor blockers （ARBs）. The docking results reveal that model 0020 possesses good affinities with these docked ARBs which are in accordance with both the IC50 inhibitor values and their curative effects. The results also show more potent interactions between the model 0020 and its ARBs than those of ever reported results, such as hydrogen bonds, hydrophobic interactions, and especially cation-n interactions and π-π interactions which have never been reported before. This may reveal that the structure of the model 0020 is quite close to its real crystal structure and the model 0020 may have the potential to be used for structure based drug design：
基金supported by National Basic Research Program of China(973 Program,No.2015CB554501)Shang hai Leading Academic Discipline Project(No.S30304)+2 种基金Youth Project of Anhui Provincial Natural Science Foundation(No.1508085QH160)Youth Scientific Research Fund Project of Anhui University of Chinese Medicine(No.2014qn004)Innovation Team Project of Scientific Research Platform for Universities in AnhuiProvince(No.2015TD033)~~
文摘Objective： To observe the effect of moxibustion therapy on heme oxygenase-1（HO-1） and monocyte chemoattractant protein-3（MCP-3） protein expressions in the colonic mucosa of rats with Crohn＇s disease（CD）, and to explore the intestinal mucosal immune mechanism of moxibustion therapy in treating CD. Methods： The CD rat model was established using the internationally accepted Morris method. The rats were randomly divided into a model group, a herbal cake-partitioned moxibustion group, a mild moxibustion group, a cigarette moxibustion group and a hot compress group, which were compared with the normal group. Except the normal group and the model group, rats in the other groups accepted different moxibustion therapies on bilateral Tianshu（ST 25）. Hematoxylin-eosin（HE） staining was conducted and the pathological changes of the colon were observed under light microscope; the expressions of HO-1 and MCP-3 protein in rat＇s colonic mucosa were determined by immunohisto-chemistry. Results： Compared with the normal group, rats in the model group showed mucosal defect, villus destruction or loss, submucosal congestion and edema, glandular destruction or disappearance, reduced goblet cells, ulcer formation, significantly increased positive target area and positive target integral optical density of HO-1 and MCP-3 protein expression（all P〈0.01）. After treatment, compared with the model group, colonic mucosa was significantly improved in the herbal cake-partitioned moxibustion group and the mild moxibustion group, which mainly showed that the intestinal glands were arranged regularly, ulcer surfaces were covered by the neoformative epitheliums, or intestinal ulcers were replaced by the nascent granulation tissue, and submucosal edema was alleviated, with a small amount of inflammatory cell infiltration. The total areas and the integral optical densities of the positive targets for rat＇s colonic mucosa HO-1 and MCP-3 protein expressions were decreased（all P〈0.01）. Compared with the cigarette moxibustion group and the hot compress group, the total areas and the integral optical densities of the positive targets for rat＇s colonic mucosa HO-1 and MCP-3 protein expressions were significantly decreased（all P〈0.01） in the herbal cake-partitioned moxibustion group and the mild moxibustion group. Conclusion： Herbal cake-partitioned moxibustion and mild moxibustion can significantly improve the inflammatory response of colonic mucosa in CD rats. It can down-regulate the expressions of HO-1 and MCP-3 proteins in the colonic mucosa of CD rats, which may be one of the mechanism in intestinal mucosal immunity caused by moxibustion therapy.
