Effect of electroacupuncture on cGAS/STING/NLRP3 pathway of the cerebral cortex in rats with cerebral ischemia reperfusion injury

ObjectiveTo observe the effect of electroacupuncture （EA） on cyclic GMP-AMP synthase （cGAS）/stimulator of interferon genes （STING）/NOD-like receptor family pyrin domain containing 3 （NLRP3） pathway of the cerebral cortex in rats with cerebral ischemia reperfusion injury and investigate the underlying mechanisms of EA in improving cerebral ischemia reperfusion injury.MethodsA total of 45 SD rats were randomly assigned into sham-operation group， model group and EA group， with 15 rats in each group. The modified thread embolism method was used to establish the model of cerebral ischemia reperfusion injury. Rats in the EA group received EA at “Baihui” （GV20）， “Fengfu” （GV16）， and “Dazhui” （GV14） for 20 min， once daily for 7 consecutive days. The modified neurological severity score （mNSS） was used to assess the neurological deficit condition. TTC staining was used to detect the percentage of cerebral infarction. HE staining was used to detect the pathological morphology in the cerebral cortex of infarcted side of rats. TUNEL staining was used to detect the apoptosis rate of cerebral cortical nerve cells. ELISA was used to detect the contents of interleukin （IL）-1β and IL-18 in the cerebral cortex of infarcted side. Western blot and qPCR were respectively used to detect the protein and mRNA expressions of cGAS， STING， TANK binding kinase-1（TBK1）， Interferon regulatory factor 3（IRF3） and NLRP3 in the cerebral cortex of infarcted side.ResultsIn comparison with the sham-operation group， the mNSS and the percentage of cerebral infarction were increased （P<0.01）； there were structural disorders and neuronal damage in the cerebral cortex of infarcted side； the apoptosis rate of nerve cells was increased （P<0.01）， the contents of IL-1β and IL-18 were increased （P<0.01）， and the protein and mRNA expressions of cGAS， STING， TBK1， IRF3 and NLRP3 were elevated （P<0.01） in the model group. In comparison with the model group， the mNSS and the percentage of cerebral infarction were decreased （P<0.01）； the pathological damage was alleviated； the apoptosis rate of nerve cells was decreased （P<0.01）， the contents of IL-1β and IL-18 were decreased （P<0.01）， and the protein and mRNA expressions of cGAS， STING， TBK1， IRF3 and NLRP3 were reduced （P<0.01） in the EA group.ConclusionEA can improve cerebral ischemia reperfusion injury， which is related to the inhibition of the cGAS/STING/NLRP3 pathway and inflammatory response in the cerebral cortex.