Neuroprotective Effect of Picroside Ⅱ on Vascular Dementia Rats by Regulating the JAK2/STAT3 Signaling Pathway
Objective To investigate the neuroprotective effect of picroside Ⅱ on vascular dementia (VD) rats by regulating the JAK2/STAT3 signaling pathway. Methods SD rats were randomly separated into the sham operated group,the model group,picroside Ⅱ low-dose group,picroside Ⅱ high-dose group,and picroside Ⅱ high-dose+colivelin (the JAK2/STAT3 signaling pathway agonist)group. Zea-Longa method was applied to evaluate the neural function of rats. Luxol fast blue (LFB) staining method was applied to observe the morphology of the myelin sheaths in corpus callosum of each group. ELISA method was applied to detect the levels of TNF-α,IL-6,and IL-10 in serum. The morphological changes of hippocampal tissue were observed by HE staining. The commercialized reagent kits were applied to detect the levels of BDNF,MDA,SOD,and CAT in hippocampal tissue. Western Blot was applied to detect the protein expression of Cleaved-Caspase-3,MBP,Olig1,p-JAK2/JAK2,and p-STAT3/STAT3 in hippocampal tissue. Results Compared with the sham operated group,the rats in the model group showed significant damage to the myelin sheath structure in the corpus callosum and the CA1 region in the hippocampal tissue. The neurological function score,serum TNF-α and IL-6 levels,as well as the protein expression of Cleaved-Caspase-3,p-JAK2/JAK2,and p-STAT3/STAT3 and MDA level in hippocampal tissues were significantly increased,the serum IL-10 level,BDNF,SOD,and CAT levels in hippocampal tissues,and the proteins expression of MBP and Olig1 were significantly reduced (P<0.05). Compared with the model group,the damage to the myelin sheath structure in the corpus callosum and the CA1 area of the hippocampal tissue in the picroside Ⅱ low-and high-dose groups was significantly reduced. The neurological function score,serum TNF-α and IL-6 levels,the protein expression of Cleaved-Caspase-3,p-JAK2/JAK2,and p-STAT3/STAT3 and MDA level in hippocampal tissues were significantly reduced,while the serum IL-10 level,BDNF,SOD,and CAT levels in hippocampal tissues,as well as the protein expression of MBP and Olig1 were significantly increased (P<0.05). All indices exhibited a dose-dependent improvement (P<0.05). Compared with picroside Ⅱ high-dose group,colivelin was able to alleviate the neuroprotective effect of picroside Ⅱ on VD rats(P<0.05). Conclusion Picroside Ⅱ may reduce oxidative stress,inflammation,and nerve tissue damage,repair damaged myelin sheaths,and improve neurological function in VD rats by inhibiting the JAK2/STAT3 signaling pathway.