Protective effects of Sennoside A on hypoxic-ischemic brain injury in neonatal rats
HU Shuli
ZHANG Hongwei
QIN Yanfen
ZHENG Leiju
WAN Biqiong
Li Zhou
ZHANG Rui
Abstract：Objective To investigate the protective effects of Sennoside A(SA)on hypoxic-ischemic brain damage(HIBD)in neonatal rats and its potential molecular mechanisms.Methods Fifty healthy 7-day-old SD rats were randomly divided into five groups:sham operation group,HIBD group,low-dose SA treatment group(SA-L,25 mg/kg),medium-dose SA treatment group(SA-M,50 mg/kg),and high-dose SA treatment group(SA-H,100 mg/kg).The HIBD model was established by left common carotid artery ligation combined with hypoxia,and rats in the treatment groups were administered different doses of SA.Histopathological changes in the hippocampal brain tissue were observed using HE staining.Brain function was assessed by brain index,brain water content,and neurological deficit score.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in brain tissue were detected using kits.The mRNA levels of interleukin-10(IL-10),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in brain tissue were detected by qRT-PCR.The levels of IL-10,IL-6,and TNF-α in peripheral blood were measured by ELISA.Cell apoptosis in brain tissue was detected by TUNEL,and the expression of apoptosis-related proteins Bax,Bcl-2,and cleaved Caspase-3 was detected by Western Blot.Results Compared with the sham operation group,,in terms of the brain function,the brain index,the brain water content and neurological deficit score of the HIBD group increased(P<0.05).In terms of oxidative stress,the SOD content in the HIBD group decreased(P<0.05),while its MDA content increased(P<0.05).Regarding inflammation-related indicators,the levels of IL-6 and TNF-α in brain tissue and peripheral blood of the HIBD group increased(P<0.05),while its IL-10 level decreased(P<0.05).In terms of apoptosis indicators,the number of apoptotic cells in the hippocampal brain tissue of the HIBD group increased(P<0.05),its levels of Bax and cleaved Caspase-3 proteins increased(P<0.05),and the Bcl-2 protein level decreased(P<0.05).In the SA treatment groups,no significant differences were observed in the SA-L group compared with the HIBD group.However,in the SA-Mand SA-L groups,the brain index,brain water content,and neurological defect score decreased(P<0.05),SOD content increased(P<0.05),MDA content decreased(P<0.05),the levels of IL-6 and TNF-α in tissue and peripheral blood decreased(P<0.05),IL-10 content increased(P<0.05),the number of apoptotic cells in the hippocampal brain tissue decreased(P<0.05),the expression of Bax and cleaved Caspase-3 was downregulated(P<0.05),and the expression of Bcl-2 was upregulated(P<0.05).The effects of high-dose SA were more significant.Conclusions SA can inhibit oxidative stress reactions,promote antioxidant effects in HIBD rats,alleviate immune disorders,and inhibit apoptosis in brain tissue by downregulating pro-apoptotic protein expression.The results of this study provide a theoretical basis for the clinical application of SA in the treatment of hypoxic-ischemic brain damage-related diseases.
Keywords：Sennoside AHypoxic ischemic brain injuryInterleukin-6AntioxidantApoptosis
Publication Date：2025-06-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：8( 23-30 )