SIRT1-mediated p53 deacetylation inhibits ferroptosis and alleviates heat stress-induced lung epithelial cells injury.

OBJECTIVE: Acute lung injury (ALI) is a common complication of heat stroke (HS) and a direct cause of death. However, the mechanism underlying ALI following HS remains unclear. METHOD: To investigate whether ferroptosis is involved in HS-ALI. We established a HS model of mice and mouse lung epithelial-2 cells (MLE-2). The severity of lung injury was measured by H&E staining, the wet-to-dry lung weight ratio, and Transmission electron microscopy. Potential markers of ferroptosis Fe2+, malondialdehyde (MDA), hydroxynonenal (4-HNE) and lipid peroxidation were detected. The percentages of cell death and viability induced by HS were assessed by LDH and CCK8 assays. SLC7A11, ACSL4, GPX4, SIRT1, p53, and p53 K382 acetylation levels were measured by Western blot. RESULTS: The administration of ferroptosis inhibitor ferrostatin-1(Fer-1) could significantly ameliorate lung injury, inhibiting levels of MDA and 4-HNE, and ameliorating HS-induced increased ACSL4, decreased SLC7A11 and GPX4, suggesting ferroptosis was involved in HS-induced ALI in vivo and in vitro. Moreover, SIRT1 expression decreased, and p53 K382 acetylation levels increased in MLE-2 cells. Activation of SIRT1 could improve lung epithelial ferroptosis caused by HS in vivo ang in vitro. Besides, the activation of SIRT1 could significantly reduce the p53 K382 acetylation levels, suggesting that activation of SIRT1 could prevent ferroptosis via inhibiting p53 acetylation. CONCLUSION: These findings substantiate the vital role of the SIRT1/p53 axis in mediating ferroptosis in HS-ALI, suggesting that targeting SIRT1 may represent a novel therapeutic strategy to ameliorate ALI during HS.

Effect of electro-acupuncture at Foot-Yangming Meridian on somatostatin and expression of somatostatin receptor genes in rabbits with gastric ulcer.

AIM: To discuss the protective effect of electroacupuncture at the Foot-Yangming Meridian on gastric mucosal lesion, somatostatin (SS) and the expression of SS receptor genes (SSR(1)mRNA ) in rabbits with gastric ulcer and to further explore the relative specificity of meridians and viscera at gene expression level. METHODS: Forty rabbits were randomly divided into control group (A), gastric ulcer model group (B), Foot-Yangming Meridian group (C), Foot-Shaoyang Meridian group (D) and Foot-Taiyang Meridian group (E). The gastric ulcer model was prepared by infusing alcohol into stomach. Groups C-E were treated with electro-acupuncture at points along the above meridians using meridian stimulating instruments for 7 d respectively. By the end of treatment, the index of gastric ulcer was determined, the amount of epidermal growth factor(EGF) and somatostatin was measured by radioimmunoassay (RIA). SS-R(1)mRNA expression in gastric mucosa was determined by RT-PCR. RESULTS: The value of EGF in model group was obviously lower (73.6+/-14.8 vs 91.3+/-14.9 pg/mL, P<0.01) than that in control group. The index of gastric ulcer, content of SS and expression of SSR1mRNA in gastric mucosa were significantly higher than those in control group (24.88+/-6.29 vs 8.50+/-2.98 scores, P<0.01; 2978.6+/-587.6 vs 1852.4+/-361.7 mIU/mL, P<0.01; 2.56+/-0.25 vs 1.04+/-0.36, P<0.01). The value of EGF in Foot-Yangming Meridian group was higher than that in model group (92.2+/-6.7 vs 73.6+/-14.8 pg/mL, P<0.01). The index of gastric ulcer, content of SS and expression of SS-R(1)mRNA in gastric mucosa were significantly lower than those in control group (10.88+/-3.23 vs 24.88+/-6.29 scores, P<0.01; 1800.2+/-488 vs 2978.6+/-587.6 mIU/mL, P<0.01; 1.07+/-0.08 vs 2.56+/-0.25 mIU/mL, P<0.01). Compared to the model group, the content of SS and expression of SSR1mRNA in gastric mucosa in Foot-Shaoyang Meridian group decreased (2441.0+/-488.vs 2978.6+/-587.6 mIU/mL, P<0.05;1.73+/-0.16 vs 2.56+/-0.25 mIU/mL, P<0.01). But the above parameters in Foot-Taiyang Meridian group did not improve and were significantly different from those in Foot-Yangming Meridian group (P<0.05). CONCLUSION: Electro-acupuncture at Foot-Yangming Meridian can protect gastric mucosa against injury. The mechanism may be related to the regulation of brain-gut peptides and the expression of SSR(1)mRNA.