从多胺及细胞连接蛋白角度探讨四君子汤防治胃黏膜损伤的作用机制

The Mechanism of Sijunzi Decoction in Preventing Gastric Mucosal Injury from the Perspective of Polyamines and Cell Junction Proteins

目的:观察四君子汤水提物对吲哚美辛所致大鼠胃黏膜损伤的影响,从多胺及其调控的紧密连接和粘附连接蛋白表达角度探讨四君子汤防治胃黏膜损伤的作用机制。方法:大鼠皮下注射吲哚美辛(40 mg/kg)7 h后处死,计算各组胃黏膜损伤大体评分,组织切片HE染色进行胃黏膜损伤病理评分,刮取胃黏膜并用柱前衍生HPLC法检测胃黏膜多胺(腐胺、精脒、精胺)含量、Western blot法及免疫组化法检测胃黏膜相关蛋白表达。结果:①四君子汤水提物对模型大鼠胃黏膜损伤有防治作用,大体和病理评分显著低于模型组(P<0.05或P<0.01);②四君子汤水提物有提高模型大鼠胃黏膜多胺(精脒)含量的作用;③四君子汤水提物能提高造模大鼠胃黏膜紧密连接蛋白(ZO-1、Occludin、Claudin-3)和粘附连接蛋白(E-cadherin、α-catenin)表达(P<0.05或P<0.01),而对粘附连接蛋白β-catenin表达无明显影响。结论:四君子汤水提物防治吲哚美辛所致大鼠胃黏膜损伤的作用机制与影响胃黏膜多胺及调控紧密连接和粘附连接蛋白表达有关。

Objective:To observe the effects of Sijunzi decoction on gastric mucosal injury induced by indomethacin in rats,and to explore the mechanism of Sijunzi decoction in preventing and treating gastric mucosal injury from the perspective of polyamines and its regulation in the tight junction and adhesion junction proteins expressing.Methods:Rats were injected subcutaneously with indomethacin(40 mg/kg)and killed after 7 h.The scores of the gastric mucosa damage in each groups were calculated in general.Histological sections were stained with HE for pathological score of gastric mucosal injury.The gastric mucosa was scraped off and the contents of gastric mucosa polyamines were detected by pre-column HPLC.Western blot and immunohistochemical methods were used to detect the expressions of related proteins in gastric mucosa.Results:①Sijunzi decoction aqueous extract had preventive effect on gastric mucosal injury,and its macroscopicscore and pathological scores were lower than those of model group(P<0.05 or P<0.01).②Sijunzi decoction aqueous extract could increase the content of gastric mucosal polyamine(spermidine)in model rats.③Sijunzi decoction aqueous extract could improve the expressions of tight junction proteins(ZO-1,Occludin,Claudin-3)and adhesion junction proteins(E-cadherin,α-catenin)(P<0.05 or P<0.01)in gastric mucosal of model rats,but the expression of adhesive junction protein β-catenin had not significantly effect.Conclusion:The mechanisms of Sijunzi decoction aqueous extract on the prevention and treatment of gastric mucosal injury induced by indomethacin in rats are related to its influence on gastric mucosal polyamines and its regulations on the expressions of tight junction and adhesion junction proteins.