| 引用本文: | 潘海春,汪玲羽,顾赞华.胃复春胶囊通过抑制AQP3调节炎症性水液代谢障碍改善大鼠急性胃溃疡[J].中国现代应用药学,2023,40(6):765-772. |
| PAN Haichun,WANG Lingyu,GU Zanhua.Weifuchun Capsule Improves Acute Gastric Ulcer in Rats by Inhibiting AQP3 and Regulating Inflammatory Water Metabolism Disorder[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(6):765-772. |
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| 摘要: |
| 目的 通过观察胃复春胶囊对大鼠胃溃疡组织炎症因子和水通道蛋白(aquaporins，AQPs)表达的影响，从水液代谢角度阐释胃复春胶囊对胃溃疡的干预作用，为临床上胃复春胶囊用于胃溃疡的防治提供实验和理论依据。方法 取体质量为190~210 g的雄性SD大鼠40只，按照体质量随机分为假手术组(生理盐水)、模型组(生理盐水)、阳性对照组(雷尼替丁30 mg·kg-1)和胃复春高、低剂量组(1 000，500 mg·kg-1)5组。造模前，各组大鼠分别以口服灌胃方式给予相应剂量的药物。连续给药3 d后行乙酸致大鼠胃溃疡模型手术。继续给药5 d后处理大鼠，解剖收集胃液，检测胃液量和胃蛋白酶活性。取胃组织用于大体和病理组织学观察。检测胃组织中超氧化物歧化酶(superoxide dismutase，SOD)、丙二醛(malondialdehyde，MDA)和炎症因子的水平，RT-PCR法检测胃组织中AQPs mRNA的表达情况，免疫荧光法检测胃组织中AQP3蛋白的表达情况。分离各组大鼠胃壁细胞，共聚焦显微镜进一步确认胃壁细胞中AQP3的表达水平。结果 胃溃疡模型组大鼠胃溃疡、糜烂明显，伴有出血点；胃复春高、低剂量组大鼠胃黏膜溃疡、糜烂有不同程度的改善。病理组织学可见，模型组黏膜水肿糜烂，炎性细胞浸润，固有层腺体破坏，间质充血等典型胃溃疡症状；胃复春不同剂量组对胃溃疡特征性病变有显著的改善作用。模型组胃蛋白酶活性显著升高，胃复春高、低剂量组和阳性对照组胃蛋白酶活性均下降。此外，胃复春胶囊可显著减低胃溃疡大鼠胃液分泌量，抑制胃蛋白酶活性，提高胃抗氧化酶活性，降低血清炎症因子水平。通过RT-PCR和免疫荧光实验可见，胃复春胶囊对胃溃疡组织AQP3 mRNA和蛋白水平的表达均有显著调控作用，进一步分离胃壁细胞，证实胃复春胶囊对胃壁细胞中的AQP3表达有显著抑制作用。结论 胃复春胶囊能显著改善大鼠胃溃疡症状，提高机体抗氧化水平，调节炎性水液代谢障碍，其作用机制可能与抑制胃壁细胞中AQP3的表达有关。 |
| 关键词: 胃复春胶囊 胃溃疡 水液代谢 炎症 |
| DOI：10.13748/j.cnki.issn1007-7693.20220119 |
| 分类号:R285.5 |
| 基金项目: |
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| Weifuchun Capsule Improves Acute Gastric Ulcer in Rats by Inhibiting AQP3 and Regulating Inflammatory Water Metabolism Disorder |
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PAN Haichun1, WANG Lingyu2, GU Zanhua3
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1.Hangzhou Huqing Yutang Pharmaceutical Co., Ltd., Hangzhou 311199, China;2.Department of Gastroenterology, the Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310061, China;3.Department of Internal Medicine, Nanxun District Hospital of Traditional Chinese Medicine, Huzhou 313009, China
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| Abstract: |
| OBJECTIVE To explain the intervention effect from the perspective of water metabolism of Weifuchun capsule(WFC) on gastric ulcers by observing the effect of WFC on the expression of inflammatory factors and aquaporins(AQPs) in rat gastric ulcer tissue, providing the experimental and theoretical basis for the clinical prevention and treatment of gastric ulcer with WFC. METHODS A total of 40 male SD rats weighing 190-210 g were randomly divided into the following 5 groups according to their body weight:sham operation group(normal saline), model group(normal saline), positive control group(ranitidine 30 mg·kg-1), WFC high-dose group(1 000 mg·kg-1) and WFC low-dose group(500 mg·kg-1). Before modeling, rats in each group were given corresponding doses of drugs by oral gavage. After continuous administration for 3 d, acetic acid-induced gastric ulcer model surgery in rats was performed. After administration for successive 5 d, the rats were treated. The gastric juice was collected for detecting the amount of gastric juice and pepsin activity. The gastric tissue was taken for gross and histopathological observation. The levels of superoxide dismutase(SOD), malondialdehyde(MDA), and inflammatory factors in gastric tissue were detected, the expression of AQPs mRNA was detected by RT-PCR, and the expression of AQP3 protein was detected by immunofluorescence. The parietal cells of rats in each group were separated, and the confocal microscope was used to further confirm the expression level of AQP3 and the release of inflammatory factors. RESULTS Rats in the gastric ulcer model group had obvious gastric ulcers and erosions, accompanied by bleeding points; rats in the high- and low-dose groups of WFC had improved gastric mucosal ulcers and erosions to varying degrees. According to histopathology, the model group showed mucosal edema and erosion, inflammatory cell infiltration, destruction of lamina propria glands, and mesenchymal congestion; different dose groups of WFC had a significant improvement effect on the characteristic lesions of gastric ulcer. The pepsin activity in the model group was significantly increased, which was decreased in the high- and low-dose groups and in the positive control group. In addition, WFC could significantly reduce the secretion of gastric juice in rats with gastric ulcers, inhibit the activity of pepsin, increase the activity of gastric antioxidant enzymes, and reduce the level of serum inflammatory factors. The RT-PCR and immunofluorescence results showed that WFC capsules had a significant regulatory effect on the expression of AQP3 mRNA and protein in gastric ulcer tissues. The gastric parietal cells were further isolated, and it was confirmed that WFC capsules had a significant inhibitory effect on the expression of AQP3 in parietal cells. CONCLUSION WFC capsule can significantly improve the symptoms of gastric ulcers in rats, increase the body's antioxidant level, and regulate inflammatory water metabolism disorders. Its mechanism of action may be related to the inhibition of AQP3 expression in gastric parietal cells. |
| Key words: Weifuchun capsule gastric ulcer water and fluid metabolism inflammation |
