Abstract:

Objective To discuss the effect of triptolide （TP） on hippocampal neuron injury in neonatal rats with hypoxic-ischemic encephalopathy （HIE）， and to clarify its related mechanism based on the phosphatase and tensin homolog deleted on chromosome 10 （PTEN）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） signaling pathway. Methods Twelve neonatal rasts were randomly selected as sham operation group； another 58 neonatal rats were usedto establish models.The HIE model was established by right common carotid artery ligation combined with hypoxic exposure. The 48 successful modeling rats were randomly divided into HIE group， low dose of TP group （L-TP group）， high dose of TP group （H-TP group） and high dose of TP+Ad-PTEN group （H-TP+Ad-PTEN group）， with 12 rats in each group. The neurobehavioral function of the rats in various groups was evaluated； triphenyltetrazolium chloride（TTC） staining was used to observe the cerebral infarction status of the rats in various groups； HE staining was used to observe the pathological morphology of the hippocampal CA1 region of the rats in various groups； kits were used to detect the serum levels of interleukin-6 （IL-6）， interleukin-8（IL-8） and tumor necrosis factor-α （TNF-α） of the rats in various groups； kits were used to detect the activities of superoxide dismutase （SOD） and catalase （CAT） and the levels of glutathione （GSH） in brain tissue of the rats in various groups； terminal deoxynucleotidyl transferase dUTP nick end labeling（TUNEL） method was used to detect the number of positive neurons of the rats in various groups； Western blotting method was used to detect the expression levels of apoptosis-related proteins， PTEN， PI3K and AKT proteins， and phosphorylated PI3K（p-PI3K）/PI3K and phosphorylated AKT（p-AKT）/AKT ratios were caculated in brain tissue of the rats in various groups. Results ompared with sham operation group， the neurological function score， serum levels of IL-6， IL-8 and TNF-α， the number of positive nenrrons in hippocampal tissue， and the expression levels of B cell lymphoma-2（Bcl-2)-associated X protein（Bax）， Cytochrome c（Cyt c）， cysteinyl aspartate-specific proteinase-8（Caspase-8）， cysteinyl aspartate-specific proteinase-3（Caspase-3） and PTEN proteins in brain tissue of the rats in HIE group were increased （P<0.05）； the activities of SOD and CAT， the level of GSH， the expression level of Bcl-2 protein， p-PI3K/PI3K and p-AKT/AKT ratios in brain tissue of the rats in HIE group were decreased （P<0.05）. Compared with HIE group， the activities of SOD and CAT， the levels of GSH， the expression levels of Bcl-2 protein， and the p-PI3K/PI3K and p-AKT/AKT ratios in brain tissue of the rats in L-TP group and H-TP group were increased （P<0.05）， and the expression levels of Bax，Cyt c，Caspase-8，Caspase-3，and PTEN proteins were decreased （P<0.05）. Compared with H-TP group， the activities of SOD and CAT， the level of GSH， the expression level of Bcl-2， and the p-PI3K/PI3K and p-AKT/AKT ratios in H-TP+Ad-PTEN group were decreased （P<0.05）， and the expression levels of Bax，Cyt c，Caspase-8，Caspase-3， and PTEN proteins were increased （P<0.05）. Conclusion TP can inhibit PTEN expression and activate the PI3K/AKT signaling pathway， thereby reducing HIE-mediated hippocampal neuron injury， apoptosis， inflammatory response and oxidative stress in the neonatal rats， and plays a protective role against hippocampal neuron injury induced by HIE.

Key words: Hypoxic-ischemic encephalopathy, Triptolide, Apoptosis, Inflammation, Oxidative stress