Effect of Polydatin on Neuroinflammation in Rats with Hypertensive Intracerebral Hemorrhage via Regulation of the JAK2/STAT3 Signaling Pathway
Objective:To investigate the effect of polydatin on neuroinflammation in rats with hyperten-sive intracerebral hemorrhage(HICH)through the regulation of the JAK2/STAT3 signaling pathway.Meth-ods:Sprague-Dawley rats were randomly divided into six groups:sham operation group,HICH group,and three polydatin dosage groups(low,medium,and high;Polydatin-L,Polydatin-M,Polydatin-H;25mg/kg,50mg/kg,100mg/kg respectively),and the Polydatin-H+JAK2/STAT3 pathway activator(Colivelin)group(100mg/kg Polydatin+1 mg/kg Colivelin),with 10 rats in each group.The sham operation group un-derwent blunt separation of bilateral renal arteries and injection of saline,while the other groups were induced with HICH by bilateral renal artery constriction using silver clips and autologous blood injection,followed by respective drug or saline interventions.Three days later,modified Neurological Severity Score(mNSS)and brain water content were measured.Serum was isolated for ELISA to detect levels of interleukin(IL)-1β and tumor necrosis factor(TNF)-α.Brain tissue was isolated for pathological changes observed by HE staining,IL-10 and IL-4 expression detected by immunofluorescence,and JAK2/STAT3 signaling pathway-related protein expression analyzed by Western blot.Results:Compared with the sham operation group,the HICH group showed significantly increased mNSS score,serum IL-1β,TNF-α levels,brain water content,p-JAK2/JAK2,and p-STAT3/STAT3 expressions,but decreased IL-10 and IL-4 expressions(P<0.05).Compared with the HICH group,the Polydatin-L,Polydatin-M,and Polydatin-H groups had significantly decreased mNSS scores,serum IL-1β,TNF-α levels,brain water content,p-JAK2/JAK2,and p-STAT3/STAT3 expressions,but increased IL-10 and IL-4 expressions,with statistically significant differences among the different concentrations of polydatin(P<0.05).Compared with the Polydatin-H group,the Polydatin-H+Colivelin group had significantly increased mNSS score,serum IL-1β,TNF-α levels,brain water content,p-JAK2/JAK2,and p-STAT3/STAT3 expressions,but decreased IL-10 and IL-4 expressions(P<0.05).Conclusion:Polydatin inhibits the JAK2/STAT3 signaling pathway,reduces pro-inflammatory cytokine lev-els,enhances anti-inflammatory levels,and alleviates pathological damage in rats with HICH.