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1.The enhancement effect of domperidene on esophagus and lower esophageal sphincter

Lu ZHOU ; Lijian WANG ; Bo YUANG ; Hang ZHANG

Chinese Journal of Digestion 2008;28(9):594-599

Objective To observe the prokinetic effect of domperidone on esophagus and lower esophageal sphincter (LES), and compare its effect with that of mosapride and cisapride. Methods In vivo experiments: forty rats were divided into control, domperidone, mosapride, and eisapride groups. Strain gauges were planted in proximal esophagus, distal esophagus and LES to record the activities of esophagus and LES in conscious rat. In vitro experiments: in the thermostatic muscle bath, the prokinetic effect of domperidone, mosapride, and cisapride on the contractility of rat muscle strips from esophagus body and LES were recorded by tone-transducers. Results In vivo experiments, ① In the interdigestive period of resting conscious rats, only mild contraction activities were recoded in esophagus bodies. In LES, typical interdigestive migrating motor complex (MMC) with phase Ⅰ,Ⅱ,Ⅲ,and Ⅳ was recorded. The contraction amplitude of LES was much greater than esophagus body. ② Domperidone significantly enhanced the contraction of esophagus body and LES. The mean contraction amplitude of proximal esophagus, distal esophagus, and LES increased by 63.24%±7.17%, 75.54%±5.27%, and 85.81%±6.02%, respectively, compared with controls. The prokinetic effect showed a dose-effect relation. Mosapride at the same dosage increased the mean contraction amplitude of proximal esophagus, distal esophagus, and LES by 29. 71%±4.15%, 40.15%±3.30%, and 35.24%±5.36%, respectively, compared with controls. The prokinetic effects of mosapride on esophagus and LES were much less than domperidone. Cisapride at the same dosage increased the mean contraction amplitude of proximal esophagus, distal esophagus, and LES by 59.84%±6.55%, 70.11%±5.62%, and 75.13%± 5.10%, respectively, compared with controls. The prokinetic effects of cisapride were similar as domperidone. In vitro experiments. ① Domperidone perfusion could significantly increase the contraction of esophagus body and LES muscle strips by 87.74%±7.65% and 92.44±7.17%, respectively, compared with Krebs-Ringer (KR) solution perfuslon. Mosapride at the same dosage increased the mean contraction amplitude by 35.42%±5.02% and 31.12%±4.32%, respectively, compared with KR controls. The prokinetic effects of mosapride were much less than domperidone. Cisapride of the same dosage showed a similar prokinetic effect as domperidone. ② Atropine and tetrodotoxin could block the prokinetic effects of domperidone on esophagus and LES. Conclusions Domperidone can significantly enhance the esophagus body contraction and LES motility. The effects of domperidone are similar as cisapride and much greater than mosapride. The prokinetic effects of domperidone on esophagus and LES are not only through well-known dopaminergic receptor blockade, but also through the cholinergic nerves of the enteric nervous system.

2.Effect of silicon dioxide exposure on airway surface microenvironment and NEK7/NLPR3 inflammasome in rats

Wenlu HANG ; Qi WU ; Wanjun LI ; Yun BO ; Xianmei ZHOU

Journal of Preventive Medicine 2023;35(2):180-184

Objective: To examine the effect of SiO2 exposure on the airway surface microenvironment and NIMA-related kinase 7 (NEK7)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in rats. Methods: Twenty-four specific pathogen-free male rats of the SD strain were randomly divided into the control group and the model group, of 12 rats in each group. Rats in the model group were given SiO2 suspensions through disposable tracheal intubation perfusion to model silicosis in rats, while rats in the control group was perfused with the same amount of physiological saline. The pH value and glucose level were measured in the rat bronchoalveolar lavage fluid (BALF) 14 and 28 days after modeling. Lung tissues were stained with HE and Masson and the distribution of inflammatory cells and the deposition of pulmonary interstitial collagens were observed in lung tissues under a light microscope. The expression of transforming growth factor β1 (TGF-β1), collagen type Ⅰ(ColⅠ), collagen type Ⅲ (Col Ⅲ), interleukin-1β (IL-1β), NLRP3, N-terminal domain of Gasdermin D (GSDMD-NT), caspase-1, and NEK7 was quantified in lung specimens using immunohistochemistry. Results: Lower pH values were measured in rat BALF in the model group than in the control group 14 [(6.38±0.05) vs. (6.68±0.08), P<0.05] and 28 days after modeling [(6.63±0.14) vs. (6.86±0.05), P<0.05], while higher glucose levels were seen in the model group than in the control group 14 [(0.39±0.06) vs. (0.31±0.04) mg/dL, P<0.05] and 28 days after modeling [(0.39±0.08) vs. (0.31±0.06) mg/dL, P<0.05]. HE and Masson staining showed mild to moderate alveolitis and pulmonary fibrosis in rats 14 days post-exposure to SiO2, and showed moderate to severe alveolitis and pulmonary fibrosis 28 days post-exposure. Immunohistochemistry detected higher TGF-β1, ColⅠ, Col Ⅲ, IL-1β, NLRP3, GSDMD-NT, caspase-1 and NEK7 expression in rat lung tissues in the model group than in the control group (all P<0.05). Conclusions SiO2 exposure may cause changes in rat airway surface microenvironment, including BALF acidification and elevated glucose. Pyroptosis induced by activation of NEK7-associated NLRP3 inflammasome may be an important mechanism of pulmonary fibrosis caused by silicosis.

1.The enhancement effect of domperidene on esophagus and lower esophageal sphincter

2.Effect of silicon dioxide exposure on airway surface microenvironment and NEK7/NLPR3 inflammasome in rats

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