Abstract: Objective  To investigate the effects of Protein Kinase A(PKA)-PTEN induced putative kinase 1(PINK1)/E3 ubiquitin ligases(Parkin) signal pathway on apoptosis and pyroptosis of rat cortical astrocytes exposed to oxygen-glucose deprivation/resuscitation(OGD/R). 
Methods  Primary cortical astrocytes were cultured in vitro from SD neonatal ratsand seededon 6 or 96-well plates. They were divided into four groups(n=42): control group(C group), oxygen-glucosede privation group/resuscitation group(OGD/R group), and H89+OGD/R group(HO group), and H89 control group(H) group according random number table method. H89 is a specific inhibitor of PKA. OGD/Rmodel was established by 95% N2-5% CO2 and sugar-free culture-medium for 6 h and subsequently at normal culture-medium containing 5% CO2 for 24 h. At 1 h before OGD/R exposure, the cultures in HO and H group were treated with H89 10 μmol/L. C and H groups were rinsed with PBS and cultured in a normal incubator containing 5% CO2. Subsequently, the apoptosis, pyroptosis and viability of cortical astrocytes were assessed by Annexin V-FITC/(Propidium Iodide) PI, cleaved caspase-1/PI and methyl thiazolyl tetrazolium（MTT) assays, respectively. Intracellular calcium ion concentration and reactive oxygen species（ROS) content were assessed by Fluo-3/AM fluorescence and 2′, 7′-dichlorodihydrofluorescein diacetate(DCFH-DA) assays respectively. The activity of PKA was measured by enzyme-linked immunosorbent assay. The expressions in PINK1 and Parkin were measured by Western blot assay. 
Results  Compared with C group, there were significant increases of astrocytes apoptosis, pyroptosis,intracellular free calcium ion concentration, ROS content, PKA activity, and expressions of PINK1 and Parkin, but decreases of viability in OGD/R and HO group(P＜0.05). Compared with OGD/R group, there were significant decreases of astrocytes apoptosis, pyroptosis, intracellular free calcium ion concentration, ROS content, PKA activity, and expressions of PINK1 and Parkin, but increases of viability in HO group(P＜0.05). There were no significant differences in above indicators between C and H groups(P＞0.05). 
Conclusion  Inhibition of overactive PKA-PINK1/Parkin signal pathway could alleviate ratcortical astrocytes apoptosis and pyroptosis induced by OGD/R exposure.

Key words: apoptosis, astrocytes, protein kinase