Abstract Body: Aims: S-nitrosoglutathione (GSNO) is an endogenous low-molecular-weight S-nitrosothiol, involved in storing and transporting of nitric oxide. The study was aimed to test the effects of GSNO in ischemia/reperfusion (I/R) Injury through relieving thrombo-inflammation.
Methods: Male C57BL/6 mice (n=160) were 10-week-old (20-25 g) at the time of surgery. Mice were administered with carboplatin (60 mg/kg body weight) intraperitoneally to build thrombocytopenic models. The animals were randomized and coded by an independent researcher who was not involved in the data analysis. Investigators involved in the surgery and evaluation of all parameters were blinded to the experimental groups. The mice were randomly divided into four groups: 1) regular I/R models with iv. normal saline (NS), 2) regular I/R models + 1 mg/kg iv. GSNO, 3) thrombocytopenic I/R models with iv. NS, and 4) thrombocytopenic I/R models +1 mg/kg iv. GSNO. All animals received humane care in compliance with Beijing Tiantan Hospital’s guidance. Levels of P-selectins, interferon (IFN)-γ and infarct volume and were compared.
Results: Mean blood platelets count was 177 10^9/L in the mice administrated with carboplatin, and 383 10^9/L in the mice without carboplatin administration (p < 0.05). Comparing with the mice treated with NS, P-selectin in the ischemic brain tissue were significantly decreased after injected with GSNO either at 24 h (1610.5 vs. 863.0 pg/ml, p < 0.05) or at 7 d (1056.8 vs. 590.0 pg/ml, p < 0.05) in regular mice, and in thrombocytopenic mice (2874.2 vs. 2113.0 pg/ml, p < 0.05, at 24 h） and（3088.0 vs. 2373.0 pg/ml, p < 0.001, at 7 d） (Fig1). After treating with GSNO, levels of IFN-γ were decreased in regular mice (24 h: 635.4 vs. 244.8 pg/ml, p < 0.05; at 7 d: 559.2 vs. 100.0 pg/ml, p <0.05）and thrombocytopenic mice（24h: 423.0 vs. 491.8 pg/ml, p < 0.05; 7d: 319.6 vs. 155.4 pg/ml, p < 0.05）(Fig1). GSNO tended to have the effect of decreasing infarct volume in regular mice（24h: 65% vs. 79%, p = 0.11; 7d: 31% vs. 62%, p = 0.05） and thrombocytopenic mice（24h: 42% vs. 79%, p =0.06; 7d: 60% vs. 62%, p =0.69）than NS (Fig2).
Conclusions: GSNO reduced inflammation by limiting platelets activation to protect I/R injury in experimental stroke models.