木瓜提取物MGE30OA对吲哚美辛诱导的大鼠胃黏膜损伤的保护作用

Protective effects of MGE30OA extract from Chaenomeles speciosa on indomethacin-induced gastric mucosal lesion in rats

目的:探究木瓜提取物MGE30OA对吲哚美辛诱导的大鼠胃黏膜损伤的保护作用及其可能的机制。方法:将SD大鼠随机分为正常组,模型组,MGE30OA低、中、高剂量(25、50、100 mg/kg)组,每组5只。模型组灌胃4 mg/kg吲哚美辛;MGE30OA各剂量组灌胃吲哚美辛0.5 h后,灌胃相应剂量的MGE30OA;1次/d,持续14 d。末次给药后取大鼠胃黏膜组织,HE染色观察组织学表现,Western blot法检测胃组织中PI3K/AKT信号通路相关蛋白和MAPK3蛋白的表达;取全血,ELISA法检测血清TNF-α、IL-1β、IL-6、TGF-β1、IL-4、IL-10、COX-1、COX-2、PGE2水平。结果:模型组大鼠胃黏膜损伤明显,MGE30OA各剂量组胃黏膜损伤较模型组减轻。与正常组比较,模型组大鼠血清中促炎因子IL-6、IL-1β、TNF-α水平升高,抗炎因子TGF-β1、IL-4、IL-10水平降低,PGE2和COX-1水平降低,COX-2水平升高(P<0.05);胃组织中磷酸化(p-)PI3K/PI3K和p-AKT/AKT降低,MAPK3表达水平升高(P<0.05)。与模型组比较,MGE30OA各剂量组血清IL-6、IL-1β、TNF-α水平降低,IL-4、IL-10、TGF-β1水平升高(P<0.05);COX-2水平降低,COX-1及PGE2水平升高(P<0.05);p-PI3K/PI3K与p-AKT/AKT升高,MAPK3表达下调(P<0.05)。结论:MGE30OA对吲哚美辛诱导的大鼠胃黏膜损伤有较好的保护作用,其作用机制可能与调节PI3K/AKT、MAPK信号通路有关。

Aim:To investigate the protective effects of MGE30OA extracted from Chaenomeles speciosa on indomethacin-induced gastric mucosal lesion in rats and the possible mechanism.Methods:SD rats were randomly allocated into normal group,model group,and MGE30OA low,medium and high dose(25,50 and 100 mg/kg)groups.The model group was given 4 mg/kg indomethacin by gavage;the MGE30OA low,medium and high dose groups were first given indomethacin by gavage and then given corresponding dose of MGE30OA after 0.5 hour;gavage was administered once a day for 14 days.After the last administration,stomachs of these rats were taken,HE staining was performed to observe the histological manifestations of gastric mucosa,and the expressions of PI3K/AKT-related protein and MAPK3 in gastric tissues were detected by Western blot;whole blood was taken,and serum levels of TNF-α,IL-1β,IL-6,TGF-β1,IL-4,IL-10,COX-1,COX-2 and PGE2 were detected by ELISA.Results:The gastric mucosal lesion in the model group was obvious,but in each dose group of MGE30OA was significantly reduced.Compared with the normal group,the serum levels of pro-inflammatory factors IL-6,IL-1βand TNF-αincreased,and the levels of anti-inflammatory factors TGF-β1,IL-4 and IL-10 decreased,and the levels of PGE2 and COX-1 dropped and COX-2 rose in the model group(P<0.05).p-PI3K/PI3K and p-AKT/AKT in gastric tissue were reduced and MAPK3 expression was upregulated(P<0.05).Compared with the model group,serum IL-6,IL-1βand TNF-αlevels were declined,IL-4,IL-10 and TGF-β1 levels were augmented;COX-2 level fell,COX-1 and PGE2 levels grew;p-PI3K/PI3K and p-AKT/AKT were higher and MAPK3 expression was lower in each dose group of MGE30OA(P<0.05).Conclusion:MGE30OA has good protective effects on indomethacin-induced gastric mucosal lesion in rats,and the mechanism may be related to the regulation of PI3K/AKT and MAPK signaling pathway.