[Retracted] Heme Oxygenase-2 Localizes to Mitochondria and Regulates Hypoxic Responses in Hepatocytes

Figure 5

Inhibition of HO-2 exacerbates injury and inflammation in a murine hemorrhagic shock model. (a, b) Knockdown of HO-2 exacerbates hemorrhagic shock-induced serum TNF-α (275 ± 56 control siRNA versus 387 ± 67 HO-2 siRNA) and IL-6 (621 ± 87 control siRNA versus 903 ± 91 HO-2 siRNA). Units are pg/mL; compared to sham mice and compared to shock control siRNA mice. mice per group. (c, d) Liver injury and hypoxia were worse in the setting of knockdown of HO-2. Serum ALT increased from 225 ± 59 to 573 ± 102 IU/mL; mice per group (c). Hemorrhagic shock also resulted in increased tissue hypoxia as demonstrated by staining for the nitroimidazole EF5, which was also increased by HO-2 siRNA pretreatment (d). (e) Knockdown of HO-2 or nonspecific inhibition of HO activity is associated with earlier decompensation in severe hemorrhagic shock (MAP 20 mmHg). mice per group. (f) Arterial pH 30 minutes into severe hemorrhagic shock is decreased compared to control mice (7.32 ± 0.05 versus 7.18 ± 0.08 in shock control siRNA; ). This clinical shock parameter is further decreased in HO-2 siRNA-treated mice (7.03 ± 0.06; versus shock control siRNA mice). mice per group.

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