| Objective: To study the effect of intravenous gabapentin on myocardial ischemia-reperfusion injury in rats and its mechanismMethods:A total of 96 male SD rats,weighing 200-250 g,were divided into 8 groups（n=12）according to random number table method,including control（Sham group,myocardial ischemia-reperfusion injury（I/R）group,gabapentin（GBP）group,PI3 K inhibitor LY294002（LY）group,gabapentin + inhibitor（GBP+LY）group,and empty virus（GABAA Rδ-NC（Negative Control））group,lentivirus（GABAA Rδ-sh RNA）group and normal saline（NC）group.Ischemia reperfusion Injury（IRI）induced by ligation of left anterior descending coronary artery（LAD）.Hemodynamic indexes including heart rate and mean arterial pressure were observed.Arrhythmia score of rats was calculated.Myocardial infarction volume was expressed as infarct volume/risk area volume（IS/AAR）.The protein expression levels of PI3 K,P-Akt,BAX and Bcl-2 in rat myocardium were detected by Western blot.Lentivirus was injected into the spinal cord using a stereolocator,the expression of GABAA Rδ in spinal cord was detected by western blot.Rat H9C2 cell lines were randomly divided into four groups like control（CON）group and gabapentin（150mmol/L）+ OGD/R group,gabapentin（300mmol/L）+ OGD/R group and gabapentin（450mmol/L）+ OGD/R group）group.The model of oxygen and glucose deprivation/reoxygenation was established.Cell viability was detected by CCK8 method.Results: 1.Hemodynamics: Compared with Sham group,HR,MAP and RPP in other groups decreased during ischemia and reperfusion（P<0.05）;Compared with before ischemia,HR,MAP and RPP in all groups except Sham group were decreased（P<0.05）;Compared with IR group,THERE were no differences in HR,MAP and RPP in GBP group（P>0.05）;2.Arrhythmia score: Compared with I/R group,arrhythmia score in GBP group was significantly decreased（P<0.05）;Compared with GBP group,the arrhythmia score of GBP+LY group and GABAA Rδ-sh RNA group was increased（P<0.05）,while the arrhythmia score of NC group and GABAA Rδ-NC group was not statistically significant（P>0.05）;3.Myocardial infarction area: compared with Sham group,the infarction area in other groups increased,and the results were statistically significant（P<0.05）;Compared with I/R group,the infarct area in GBP group was decreased,and the results were statistically significant（P<0.05）;Compared with GBP group,the infarct area in GBP+LY group and GABAA Rδ-shr NA group increased,the results were statistically significant（P<0.05）;4.Related protein expression levels in myocardial tissue: Compared with Sham group,PI3 K expression,P-Akt expression,BAX expression and Bcl-2 expression were down-regulated in other groups,with statistically significant results（P<0.05）;Compared with I/R group,the protein expression levels of PI3 K and P-Akt in GBP group were increased,the expression level of BAX was decreased,and the expression level of Bcl-2 was up-regulated,with statistical significance（P<0.05）;Compared with GBP group,the expression of PI3 K and phosphorylated AKT protein in GBP+LY group was inhibited,the expression of BAX protein was up-regulated,and the expression of Bcl-2 was down-regulated,with statistical significance（P<0.05）;5.Expression of related proteins after virus injection: After virus injection,GABAA Rδ-sh RNA was detected in the spinal cord tissue of GABAA Rδ-sh RNA group compared with the blank virus group and NC group The expression of Rδ protein was significantly down-regulated（P<0.05）.Compared with Sham group,the expression of PI3 K and phosphorylated AKT protein in myocardium of lentivirus group was decreased（P<0.05）.6 cell viability :CCK8 showed no significant difference in cell viability.Conclusion Gabapentin can alleviate myocardial ischemia-reperfusion injury（in vivo）in rats.Gabapentin did not reduce H9C2 oxygen-glucose deprivation/reoxygenation injury;Gabapentin induces a cascade reaction by up-regulating GABAA Rδ,activates PI3K/AKT signaling pathway in myocardial tissue,and inhibits apoptosis to produce myocardial protection. |
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