AVE 0991 Attenuates Pyroptosis and Liver Damage after Heatstroke by Inhibiting the ROS-NLRP3 Inflammatory Signalling Pathway
The effect of AVE 0991 on the hepatic damage induced by heatstroke and Ang II. (a) Hepatic damage evaluated by analysing serum ALT at the time-point of heatstroke onset (0 h) and 4 and 9 h after heatstroke onset. The rats in the 9 h+AVE group were injected with AVE 0991 at the time-point of heatstroke onset and sacrificed after 9 h. n = 9 per group. P<0.05 compared with the sham group. #P<0.05 compared with the 9 h group. (b) The survival curves of rats with or without AVE 0991 injection after heatstroke (P=0.48). n=12 per group. (c) Hepatocellular damage was evaluated by analysing LDH in the supernatant. (d) Cell viability was evaluated using a CCK-8 assay. The sham group was not subjected to heat stress. Ang II and/or AVE 0991 were added to the BRL-3A supernatant for an additional 9 h after heat stress.P<0.05 compared with the sham group. #P<0.05 compared with the heat group. &P<0.05 compared with the heat+Ang II group. (e) (top) HE staining of liver sections from rats. Heat group: 9 h after heatstroke onset. Black rectangles indicate the area of magnification. Scale bar: 50 μm. Magnification of HE-stained liver section images (middle). The black arrow indicates necrosis. The blue arrow with a long handle indicates haemorrhage. MPO staining of liver sections (bottom). Scale bar: 200 μm. (f) Histological scores of liver sections. (g) MPO-positive cell counts of liver sections. n=6 per group. P<0.05 compared with the sham group. #P<0.05 compared with the heat group. The data are presented as the mean ± SD. All of the assays were performed in triplicate. HE: Haematoxylin-eosin; MPO: myeloperoxidase.
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