Effects of N-acetylcysteine combined with ischemic postconditioning on lung injury after myocardial ischemia-reperfusion in diabetes mice
Objective To investigate the effects of N-acetylcysteine(NAC)combined with ischemic postconditioning(IPostC)on myocardial ischemic reperfusion induced lung injury in diabetic mice.Methods 30 15-week-old male db/db diabetic mice were divided into sham operation group(D-SO group,n=10),myocardial ischemia/reperfusion group(D-I/R group,n=10)and NAC combined with ischemic postconditioning group(D-NAC+IPostC group,n=10).D-SO group mice did not receive any treatment after thoracotomy.D-I/R group was treated with left anterior descending coronary artery ligation for 60min andthenreperfusion for 15 min.In D-NAC+IPostC group,150 mg/kg NAC was intraperitoneally injected half an hour before ligation of the left anterior descending coronary artery.The intervention method of ischemia postcondition-ing was 3 cycles of reperfusion/ischemiaimmediately after 60min of ischemia,followed by 15min of reper-fusion.Blood was collected from the abdominal aorta after reperfusion,and serum C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and monocyte chemotaxis protein-1(MCP-1)levels were detec-ted.Mice were sacrificed;lung tissues were collected;and wet-dry weight(W/D)ratio was detected.The pathological changes of lung tissues were observed under light microscope,and lung injury scores were cal-culated.The levels of superoxide dismutase(SOD),glutathione(GSH)and malondialdehyde(MDA)of oxidative stress-related markers in lung tissue were determined.The expressions of hypoxia-inducing fac-tor 1α(HIF-1α)and vascular endothelial growth factor(VEGF)in lung tissue were detected by Western Blot.Results Compared with D-SO group,pathological injury of D-I/R group was serious under light mi-croscope(P<0.05);lung W/D ratio was increased(P<0.05);serum TNF-α and CRP were decreased(P<0.05);MCP-1 level was increased(P<0.05);and MDA content in lung tissue was increased(P<0.05);SOD and GSH activities were decreased(P<0.05);HIF-1α and VEGF expression were increased(P<0.05).Compared with D-I/R group,pathological injury of lung tissue in D-NAC+IPostC group was significantly reduced under microscope(P<0.05);lung W/D ratio was decreased(P<0.05);serum TNF-α and MCP-1 were decreased(P<0.05);CRP was increased(P<0.05).The content of oxidative stress factor MDA was decreased(P<0.05),the activities of antioxidant stress factors SOD and GSH were increased(P<0.05),and the expressions of HIF-1αand vascular endothelial growth factor(VEGF)were increased(P<0.05).Conclusion NAC combined with IPostC can reduce lung injury after myocar-dial I/R in diabetic mice,and the mechanism may be related to HIF-1α/VEGF signaling pathway.