Pinus massoniana needle extracts attenuate oxidative stress injury in cerebral ischemia reperfusion rats by regulating JNK3/caspase-3 signal transduction.

OBJECTIVE: To investigate the effect and mechanism of Pinus massoniana needle extracts (PNE) on oxidative stress injury in cerebral ischemia reperfusion rats. METHODS: The SD male rats were randomly divided into sham group, model control group, Edaravone (3 mg/kg) group, PNE low-dose (200 mg/kg), medium-dose (400 mg/kg) and high-dose (800 mg/kg) groups. PNE was administered by gavage for 7 d before modeling and 6 h after modeling in PNE treatment groups; Edaravone was given by intraperitoneal injection 7 d before modeling and 6 h after reperfusion. The rat model of cerebral ischemia reperfusion injury was established by middle cerebral artery occlusion method. After 24 h of reperfusion, the neurological deficit score, brain water content and cerebral infarction volume of rats were measured. The pathological changes of cerebral cortex and hippocampus were observed by HE staining, and the number of normal nerve cells was counted. The apoptosis rate of neurons in cerebral cortex was detected by TUNEL method. The content of nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) activity in ischemic brain tissue were detected. The protein expression of c-Jun N-terminal kinase (JNK) 3, phosphorylated JNK3 (p-JNK3), B-cell lymphoma protein(Bcl) -2, Bcl-2 associated X (Bax), cytochrome C and caspase-3 in cerebral cortex were detected by Western blotting method. RESULTS: Compared with the model control group, the behavioral score, brain water content and cerebral infarction volume in PNE groups were significantly reduced (all P<0.05), the pathological damage of cerebral cortex and hippocampal CA1 area was significantly alleviated, and the number of normal nerve cells in ischemic cortex and hippocampal CA1 area was increased (all P<0.05). The medium-dose PNE group had the best effect. Compared with the model control group, the apoptosis rate of cortical neurons, the content of NO and MDA in cerebral cortex, the ratio of p-JNK3/JNK3, the expression level of cytochrome C and caspase-3 protein in PNE medium-dose group were significantly reduced , and the activity of SOD, the Bcl-2/Bax ratio were significantly improved (all P<0.05). CONCLUSION: PNE ameliorates brain injury after cerebral ischemia reperfusion in rats, which may be related to scavenging NO and MDA, inhibiting oxidative stress-mediated JNK3/caspase-3 signsal transduction to inhibit neuronal apoptosis.

Human umbilical cord mesenchymal stem cells-derived exosomes transfers microRNA-19a to protect cardiomyocytes from acute myocardial infarction by targeting SOX6.

Exosomes secreted by human umbilical cord mesenchymal stem cells (hucMSCs) protect cardiomyocytes from anoxia-reoxygenation injury. But the mechanism of hucMSC-exo-microRNA (miR)-19a in acute myocardial infarction (AMI) remains unclear. For this study, cardiac function related indicators, inflammatory factors and markers of myocardial injury, cardiomyocyte injury, infarct size, and apoptosis were detected in vivo experiments. The gain-and loss-of function was performed to evaluate the effects of hucMSC-exo with down/upregulated miR-19a on AMI rats and hypoxic H9C2 cells. Western blot analysis was used to detect levels of AKT/JNK3/caspase-3 axis-related proteins. Consequently, hucMSC-exo alleviated AMI and inhibited cardiomyocyte apoptosis. miR-19a was downregulated in AMI tissues and cells, and increased after hucMSC-exo treatment. miR-19a knockdown in hucMSC-exo impaired the protective role of hucMSC-exo alone in the AMI damage. SOX6 is a target gene of miR-19a and its inhibition lightened hypoxic damage of H9C2 cells. SOX6 knockdown together with miR-19a inhibition in hucMSC-exo activated AKT and inhibited JNK3/caspase-3 axis. Taken together, hucMSC-exo protected cardiomyocytes from AMI injury by transferring miR-19a, targeting SOX6, activating AKT, and inhibiting JNK3/caspase-3 activation. This study may provide new understanding for AMI treatment.