|
|
|
| Effect of Polydatin on Neuroinflammation in Rats with Hypertensive Intracerebral Hemorrhage via Regulation of the JAK2/STAT3 Signaling Pathway |
| XU Yongjie, JIA Xiaolong, WANG Yanling, et al |
| Handan First Hospital, Hebei Handan 056002, China |
|
|
|
|
Abstract Objective: To investigate the effect of polydatin on neuroinflammation in rats with hypertensive intracerebral hemorrhage (HICH) through the regulation of the JAK2/STAT3 signaling pathway.Methods: 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 underwent 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 levels, enhances anti-inflammatory levels, and alleviates pathological damage in rats with HICH.
|
|
|
|
|
|
[1] Jolink WMT,Wiegertjes K,Rinkel GJE,et al.Location-specific risk factors for intracerebral hemorrhage:systematic review and meta-analysis[J].Neurology,2020,95(13):1807-1818.
[2] Huang Y,Zheng H,Mo M.Effect of different operation time on surgical effect and quality of life in patients with severe hypertensive intracerebral hemorrhage[J].Am Transl Res,2021,13(8):9538-9545.
[3] Xiao W,Jiang Z,Wan W,et al.miR-145-5p targets MMP2 to protect brain injury in hypertensive intracerebral hemorrhage via inactivation of the Wnt/β-catenin signaling pathway[J].Ann Transl Med,2022,10(10):571-585.
[4] Hu D,Mo X,Luo J,et al.17-DMAG ameliorates neuroinflammation and BBB disruption via SOX5 mediated PI3K/Akt pathway after intracerebral hemorrhage in rats[J].Int Immunopharmacol,2023,123(1):110698-110709.
[5] Karami A,Fakhri S,Kooshki L,et al.Polydatin:pharmacological mechanisms,therapeutic targets,biological activities,and health benefits[J].Molecules,2022,27(19):6474-6514.
[6] Lin J,Xu Y,Guo P,et al.CCL5/CCR5-mediated peripheral inflammation exacerbates blood-brain barrier disruption after intracerebral hemorrhage in mice[J].Transl Med,2023,21(1):196-214.
[7] Sha Q,Huang Y,Zhou F,et al.Effects of polydatin from Huhuang Shaoshang Liniment on oxidative damage and inflammatory response in rats with cerebral ischemia-reperfusion[J].Am Transl Res,2023,15(2):995-1006.
[8] Shao W,Zhang C,Li K,et al.Wogonin inhibits inflammation and apoptosis through STAT3 signal pathway to promote the recovery of spinal cord injury[J].Brain Res,2022,1782(1):147843-147852.
[9] Xu Z,Zhao B,Mao J,et al.Knockdown of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 protects against intracerebral hemorrhage through microRNA-146a-mediated inhibition of inflammation and oxidative stress[J].Bioengineered,2022,13(2):3969-3980.
[10] Anand S,Choudhury SS,Pradhan S,et al.Normotensive state during acute phase of hypertensive intracerebral hemorrhage[J].Neurosci Rural Pract,2023,14(3):465-469.
[11] Li CX,Li L,Zhang JF,et al.Tripartite intensive intervention for prevention of rebleeding in elderly patients with hypertensive cerebral hemorrhage[J].World Clin Cases,2021,9(33):10106-10115.
[12] Wang Y,Tian M,Tan J,et al.Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin αVβ5/AMPK signaling pathway after intracerebral hemorrhage in mice[J].Neuroinflammation,2022,19(1):82-101.
[13] Xu J,Chen Z,Yu F,et al.IL-4/STAT6 signaling facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice[J].Proc Natl Acad Sci U S A,2020,117(51):32679-32690.
[14] Chen G,Yang Z,Wen D,et al.Polydatin has anti-inflammatory and antioxidant effects in LPS-induced macrophages and improves DSS-induced mice colitis[J].Immun Inflamm Dis,2021,9(3):959-970.
[15] Zhao X,Qin J,Li H,et al.Effect of Polydatin on Neurological Function and the Nrf2 Pathway during Intracerebral Hemorrhage[J].Mol Neurosci,2020,70(9):1332-1337.
[16] Yu L,Zhang Y,Chen Q,et al.Formononetin protects against inflammation associated with cerebral ischemia-reperfusion injury in rats by targeting the JAK2/STAT3 signaling pathway[J].Biomed Pharmacother,2022,149(1):112836-112845.
[17] Shan Y,Wang L,Sun J,et al.Exercise preconditioning attenuates cerebral ischemia-induced neuronal apoptosis,Th17/Treg imbalance,and inflammation in rats by inhibiting the JAK2/STAT3 pathway[J].Brain Behav,2023,13(6):3030. |
|
|
|
2024, Vol. 30 
