关键词: 过氧化物酶体增殖物激活受体α, 乙醇, 胃黏膜慢性损伤, NF-κB

Abstract: Objective To investigate the impact and mechanism of peroxisome proliferator-activating receptor α (PPARα) deletion on long-term ethanol-induced gastric mucosal injury in mice. Methods Wild-type and PPARα-knockout mice were treated with ethanol-containing diet and control diet respectively, and randomized into 4 groups. After 16 weeks, the histopathological changes of gastric mucosa were observed. ELISA and RT-qPCR were used to detect the contents and expression of inflammatory factors in serum and gastric tissues. The serum and gastric malondialdehyde(MDA) contents were tested by commercially available kit. Western blot was performed to detect the expression of gastric NF-κB signaling pathway in mice. Results Compared with wild-type mice in ethanol- diet group,PPARα-knockout mice showed more severe gastric mucosal injury and the serum TNF-α,IL-1β and gastric MDA content were significantly increased (P＜0.05); The mRNA of the downstream target genes, TNF-α, IL-1β and ICAM-1, were all significantly increased (P＜0.05). The level of nuclear protein p65 was increased(P＜0.01). Conclusions PPARα-deficiency aggravates ethanol-induced gastric mucosal injury in mice, and the mechanism might be related to the activation of gastric NF-κB signaling pathway.

Key words: PPARα, ethanol, chronic gastric mucosal injury, NF-κB