灵芝多糖硫酸酯对大鼠脑缺血再灌注损伤的保护作用及其机制

灵芝多糖硫酸酯对大鼠脑缺血再灌注损伤的保护作用及其机制李亚巍;韩丽琴;金瑛;朱文赫
【期刊名称】《吉林大学学报（医学版）》
【年(卷),期】2017(043)004
【摘要】目的:对灵芝多糖(GLP)进行硫酸酯化分子修饰,观察灵芝多糖硫酸酯(GLPS)对大鼠脑缺血再灌注损伤的保护作用,初步探讨其作用机制.方法:硫酸酯化修饰GLP,得到GLPS;将100只SD大鼠随机分为假手术组、模型组、GLP组(40 mg·kg-1·d-1)、GLPS组(40 mg·kg-1·d-1)和尼莫地平组(1 mg·kg-1·d-1),每组20只.采用线栓法建立大鼠脑缺血再灌注模型,观察脑缺血再灌注损伤大鼠的神经功能缺损评分和脑组织含水量,检测大鼠脑组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平,ELISA法检测脑组织中匀浆中核因子kappa B(NF-κB)、肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1)和白细胞介素6(IL-6)水平,Western blotting 法检测大鼠脑组织中热休克蛋白70(HSP-70)和磷酸化的丝氨酸/苏氨酸蛋白激酶(p-Akt)表达水平.结果:与模型组比较,GLP和GLPS组大鼠神经功能评分降低(P<0.01),脑组织含水量减少(P<0.05或P<0.01),SOD活性升高(P<0.05或P<0.01),MDA 水平降低(P<0.05或P<0.01),NF-κB、TNF-α、IL-1和IL-6 水平降低(P<0.05或P<0.01),且GLPS组变化较GLP组明显(P<0.05);Western blotting检测,与模型组比较,GLP组和GLPS组大鼠脑组织中p-Akt蛋白表达水平升高(P<0.05),GLPS 组大鼠脑组织中HSP-70蛋白表达水平升高(P<0.01),而GLP组HSP-70蛋白表达水平升高效果不明显.结论:硫酸酯化修饰可以明显改善GLP对大鼠脑缺血再灌注损伤的保护作用,其作用机制可能通过调控HSP70/PI3K/Akt信号通路,抑制再灌注后继发的炎症反应,从而发挥对神经细胞的保护作用.%Objective:To modify
Ganodermalucidum polysaccharides(GLP) with sulfate and observe the protective effect of Ganodermalucidum polysaccharide sulfate (GLPS) on the cerebral ischemia reperfusion injury in the rats,and to investigate its mechanism.Methods:GLP was modified by sulfation to obtain GLPS.A total of 100 SD rats were randomly divided into sham operation group, model group, GLP g roup (40 mg·kg-1·d-1), GLPS group (40 mg·kg-1·d-1) and nimodipine group (1 mg·kg-1·d-1).The cerebral ischemia reperfusion models were established by middle cerebral artery occlusion method in the rats.The neurologic deficit score and the content of water in brain tissue of the rats with cerebral ischemia reperfusion injury were detected and the activities of superoxide dismutase(SOD) and the levels of malondialdehyde (MDA) were detected.The levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB),tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) in the brain tissue homogenate were detected by ELISA.Western blotting method was used to detect the protein expression levels of HSP70 and p-Akt in the brain tissue of the rats.Results:Compared with model group, the neurological function scores of the rats in GLP group and GLPS group were decreased(P<0.01),the water contents in brain tissue were
decreased(P<0.05), the SOD activities were increased and the MDA levels were decreased(P<0.05), and the levels of NF-κB, TNF-α, IL-1 and IL-6 were decreased(P<0.05);the effect in GLPS group was significantly better than that in GLP group(P<0.05).The results of Western blotting method showed that the p-Akt protein expression levels in the brain tissue of the rats in
GLP and GLPS groups were increased compared with model group
(P<0.05);compared with model group, the HSP-70 protein expression level in the brain tissue of the rats in GLPS group was increased(P<0.01),but the effect in GLP group was not obvious.Conclusion:Sulfation can significantly improve the protective effect of GLP on the cerebral ischemia reperfusion injury in the rats and its mechanism may be related to regulating the HSP70/PI3K/Akt signaling pathway and inhibiting the inflammatory reaction damage to the nerve cells of reperfusion.
【总页数】6页(P679-684)
【作者】李亚巍;韩丽琴;金瑛;朱文赫
【作者单位】吉林医药学院药学院药物化学教研室,吉林吉林132013;吉林医药学院药学院药物化学教研室,吉林吉林132013;吉林医药学院药学院药物化学教研室,吉林吉林132013;吉林医药学院基础医学院生物化学教研室,吉林吉林 132013【正文语种】中文
【中图分类】R285.5
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