三七总皂苷对慢性萎缩性胃炎大鼠胃黏膜损伤及炎症反应的影响及机制
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篇名: 三七总皂苷对慢性萎缩性胃炎大鼠胃黏膜损伤及炎症反应的影响及机制
TITLE: Effects of Panax notoginseng saponins on gastric mucosal injury and inflammatory response in rats with chronic atrophic gastritis
摘要: 目的 基于干细胞因子(SCF)/干细胞因子受体(c-kit)信号通路探讨三七总皂苷(PNS)对慢性萎缩性胃炎(CAG)大鼠胃黏膜损伤、炎症反应的影响及潜在机制。方法取SD雄性大鼠,以N-甲基-N′-硝基-N-亚硝基胍灌胃诱导+不规律饮食的方式构建CAG大鼠模型,并将造模成功的大鼠随机分为模型组(Model组),阳性对照-维酶素组(Positive组,250mg/kg),PNS低、高剂量组(PNS-L、PNS-H组,9、18mg/kg),PNS高剂量+SCF/c-kit抑制剂组(PNS-H+ISCK03组,18mg/kg+47mg/kg),每组8只;另取健康大鼠8只,作为对照组(Control组)。末次给药后,检测各组大鼠血清中胃泌素(GAS)、胃动素(MTL)水平和胰多肽(PP)活性,以及胃黏膜组织中肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)、IL-8水平;观察其胃黏膜组织病理变化及上皮细胞超微结构,并进行胃黏膜萎缩评分;检测其胃黏膜组织细胞凋亡情况及增殖细胞核抗原(PCNA)、核因子κBp65(NF-κBp65)、SCF、c-kit蛋白的表达情况。结果与Control组比较,Model组大鼠胃黏膜组织炎症细胞浸润明显,大量上皮细胞脱落且超微结构受损严重;胃黏膜萎缩评分、胃黏膜组织中TNF-α和IL-8水平、细胞凋亡率、NF-κBp65蛋白的表达均显著升高或上调;血清中GAS、MTL水平和PP活性,胃黏膜组织中IL-10水平,以及PCNA、SCF蛋白的表达和c-kit蛋白的磷酸化水平均显著降低或下调(P<0.05)。与Model组比较,Positive、PNS-L、PNS-H组大鼠胃黏膜组织中上述病理改变均明显好转,各定量指标均显著改善,且PNS-H组的改善较PNS-L组更显著(P<0.05);而ISCK03可显著逆转高剂量PNS对大鼠上述指标的改善作用(P<0.05)。结论PNS可通过减轻炎症反应、促进胃黏膜修复,从而改善CAG大鼠胃黏膜损伤;上述作用可能与激活SCF/c-kit信号通路有关。
ABSTRACT: OBJECTIVE To investigate the effects and potential mechanism of Panax notoginseng saponins (PNS) on gastric mucosal injury and inflammatory response in rats with chronic atrophic gastritis (CAG) via the stem cell factor(SCF)/cellular tyrosine kinase receptor(c-kit) signaling pathway. METHODS Male SD rats were used to establish a CAG rat model through intragastric administration of N -methyl- N ′-nitro- N -nitrosoguanidine combined with an irregular diet. Successfully modeled rats were randomly divided into a model group, positive control-vitacoenzyme group (Positive group, 250 mg/kg), PNS low- and high-dose groups (PNS-L and PNS-H groups, 9, 18 mg/kg), and high-dose PNS+SCF/c-kit inhibitor group (PNS-H+ISCK03 group, 18 mg/kg+47 mg/kg), with 8 rats in each group. Additionally, 8 healthy rats were selected as a control group. After the final administration, the activities of serum gastrin (GAS), motilin (MTL) and pancreatic polypeptide (PP), as well as the levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and IL-8 in gastric mucosal tissues, were measured in each group. Pathological changes of the gastric mucosal and ultrastructure of the epithelial cells were observed, and gastric mucosal atrophy was scored. Cell apoptosis in gastric mucosal tissues and the expressions of proliferating cell nuclear antigen (PCNA), nuclear factor-κB p65 (NF-κB p65), SCF and c-kit were detected. RESULTS Compared with the control group, the model group showed significantly increased inflammatory cell infiltration in the gastric mucosal, extensive epithelial cell detachment, severe ultrastructural damage, and significantly elevated or up-regulated gastric mucosal atrophy score, TNF-α and IL-8 levels in gastric mucosal, cell apoptosis rate, and NF-κB p65 protein expression. Meanwhile, serum levels of GAS and MTL, PP activity, the level of IL-10 in gastric mucosal tissue, and protein expressions of PCNA and SCF, as well as the phosphorylation level of c-kit, were significantly decreased or down-regulated ( P <0.05). Compared with the model group, Positive, PNS-L and PNS-H groups exhibited markedly improved pathological changes in the gastric mucosal and significant amelioration of the quantitative indicators, with the PNS-H group showing significantly better improvement than the PNS-L group ( P <0.05). However, ISCK03 significantly reversed the ameliorative effects of high-dose PNS on the above indicators in rats ( P <0.05). CONCLUSIONS PNS improves gastric mucosal injury in CAG rats by reducing the inflammatory response and promoting gastric mucosal repair; these effects may be related to the activation of the SCF/c-kit signaling pathway.
期刊: 2026年第37卷第08期
作者: 喻玉;石容;赵龙
AUTHORS: YU Yu,SHI Rong,ZHAO Long
关键字: 三七总皂苷;慢性萎缩性胃炎;胃黏膜损伤;炎症反应;SCF/c-kit信号通路
KEYWORDS: Panax notoginseng saponins; chronic atrophic gastritis; gastric mucosal injury; inflammatory response; SCF/c-kit
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