卒中是全球公认的致残和死亡的主要原因。构成重大挑战,特别是在发展中国家。本研究旨在评价灵芝酸(GA)对大鼠局灶性缺血性脑卒中的神经保护作用。
方法:瑞士Wistar大鼠用于本研究。大鼠大脑中动脉闭塞(MCAO)模拟短暂性局灶性缺血,其次是再灌注。各种神经参数,包括梗死面积,神经功能缺损评分,脑含水量,伊文思蓝渗漏,一氧化氮(NO),诱导型一氧化氮合酶(iNOS),乳酸脱氢酶(LDH),抗氧化剂水平,炎性细胞因子,凋亡标志物,炎症参数,和基质金属蛋白酶(MMP)水平,估计。此外,在脑组织中评估mRNA表达。
结果:GA的剂量依赖性治疗显着(P<0.001)抑制了梗死面积,神经偏转评分,脑水,埃文斯蓝色泄漏,NO,iNOS,LDH,C-X-C趋化因子受体4型(CXCR-4),单核细胞趋化蛋白-1(MCP-1),S100钙结合蛋白B(S-100β)和K+-Cl-协同转运蛋白1(KCC1)阳性细胞。GA改变了氧化应激参数的水平,如总抗氧化能力(T-AOC),8-羟基-2'-脱氧鸟苷(8-OhdG),超氧化物歧化酶(SOD),过氧化氢酶(CAT),谷胱甘肽过氧化物酶(GPx),谷胱甘肽(GSH),丙二醛(MDA);细胞因子,即。,肿瘤坏死因子-α(TNF-α),白细胞介素-1(IL-1),IL-1β,IL-6,IL-9,IL-10;炎症参数,如诱导型一氧化氮合酶(iNOS),环氧合酶-2(COX-2),前列腺素(PGE2),核因子κB(NF-κB);B细胞白血病/淋巴瘤2蛋白(Bcl-2);Bcl-2相关蛋白x(Bax),胱天蛋白酶-3;基质金属肽酶(MMP)参数,如MMP-2、MMP-3和MMP-9。GA显著抑制TRL-4、Syndecan-1、CSF、水通道蛋白-1、OCT3和RFX1。
结论:灵芝酸通过多种机制对脑缺血再灌注具有保护作用。
Stroke is recognized as a leading cause of disability and mortality worldwide, posing a significant challenge, particularly in developing countries. The current study aimed to evaluate the neuroprotective effect of Ganoderic acid (GA) against focal ischemic stroke in rats.
METHODS: Swiss Wistar rats were used for the current study. The rats were subjected to middle cerebral artery occlusion (MCAO) to simulate transient focal ischemia, followed by reperfusion. Various neurological parameters, including infarct size, neurological deficit score, brain water content, Evans blue leakage, nitric oxide (NO), inducible nitric oxide synthase (iNOS), lactate dehydrogenase (LDH), antioxidant levels, inflammatory cytokines, apoptosis markers, inflammatory parameters, and matrix metalloproteinases (MMP) levels, were estimated. Additionally, mRNA expressions were evaluated in the brain tissue.
RESULTS: Dose dependently treatment of GA significantly (P < 0.001) suppressed the infarct size, neurological deflects score, brain water, evans blue leakage, NO, iNOS, LDH, C-X-C chemokine receptor type 4 (CXCR-4), monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein B (S-100β) and K+-Cl- cotransporter 1 (KCC1) positive cells. GA altered the level of oxidative stress parameters like Total antioxidant capacity (T-AOC), 8-hydroxy-2\'-deoxyguanosine (8-OhdG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), malonaldehyde (MDA); cytokines viz., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-1β, IL-6, IL-9, IL-10; inflammatory parameters such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin (PGE2), Nuclear factor kappa B (NF-κB); apoptosis parameters like B-cell leukemia/lymphoma 2 protein (Bcl-2), Bcl-2-associated protein x (Bax), Caspase-3; matrix metallopeptidase (MMP) parameters like MMP-2, MMP-3, and MMP-9, respectively. GA remarkably suppressed the mRNA expression of TRL-4, Syndecan-1, CSF, Aquaporin-1, OCT3, and RFX1.
CONCLUSIONS: Ganoderic acid exhibited the protection against the cerebral ischemia reperfusion via multiple mechanism.