Ai Jinchao, Wan Haitong, Shu Mingchun, Zhou Huifen, Zhao Tao, Fu Wei, He Yu
Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, Zhejiang, China.
Buchang Pharmaceutical Co., Ltd., Xi'an, 710075, China.
Arch Pharm Res. 2017 May;40(5):610-622. doi: 10.1007/s12272-016-0835-4. Epub 2016 Sep 13.
Guhong injection (GHI), composed of aceglutamide and safflower aqueous extract, has been used clinically for the treatment of cerebrovascular diseases such as cerebral embolism, hemorrhage and mental deterioration. In this paper, we reported the results of the first study on the anti-inflammatory effects of GHI in murine focal cerebral ischemia-reperfusion (I/R) injury. Adult male SD rats were randomly divided into six groups: Sham group, I/R group, GHI-L group (2.5 mL/kg), GHI-M group (5 mL/kg), GHI-H group (10 mL/kg) and Nimodipine group. I/R injury was induced by middle cerebral artery occlusion (MCAO) for 1.5 h followed by reperfusion for 24 h. Compared with I/R group, rats treated with GHI showed dose dependent reductions in neurological defect scores and cerebral infarct volume. GHI obviously down-regulated nitric oxide (NO), inducible NO synthase (iNOS), myeloperoxidase (MPO), interleukin-1β (IL-1β), TNF-α (tumor necrosis factor-α) and C reactive protein (CRP) levels in serum. Moreover, histological examination by H&E staining showed that clear cell outline, less vacuolated spaces and largely surviving neurons were observed in GHI-treated rats. The immunohistochemical staining revealed that GHI administration significantly diminished the positive expressions of intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB p65 (NF-κB p65) in brain tissues. Western blot analysis for ICAM, NF-κB p65 and iNOS further solidified the above findings. All these results demonstrate that GHI exerts a strong and ameliorative effect on cerebral I/R injury in rats possibly through the inhibition of inflammation.
谷红注射液(GHI)由乙酰谷酰胺和红花水提取物组成,已在临床上用于治疗脑血管疾病,如脑栓塞、脑出血和精神衰退。在本文中,我们报告了关于GHI对小鼠局灶性脑缺血再灌注(I/R)损伤抗炎作用的首次研究结果。成年雄性SD大鼠随机分为六组:假手术组、I/R组、GHI-L组(2.5 mL/kg)、GHI-M组(5 mL/kg)、GHI-H组(10 mL/kg)和尼莫地平组。通过大脑中动脉闭塞(MCAO)1.5小时,随后再灌注24小时诱导I/R损伤。与I/R组相比,用GHI治疗的大鼠神经功能缺损评分和脑梗死体积呈剂量依赖性降低。GHI明显下调血清中一氧化氮(NO)、诱导型NO合酶(iNOS)、髓过氧化物酶(MPO)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和C反应蛋白(CRP)水平。此外,苏木精-伊红(H&E)染色的组织学检查显示,在GHI治疗的大鼠中观察到细胞轮廓清晰、空泡化空间较少且神经元大量存活。免疫组织化学染色显示,给予GHI可显著减少脑组织中细胞间黏附分子-1(ICAM-1)和核因子-κB p65(NF-κB p65)的阳性表达。对ICAM、NF-κB p65和iNOS的蛋白质印迹分析进一步证实了上述发现。所有这些结果表明,GHI可能通过抑制炎症对大鼠脑I/R损伤发挥强大的改善作用。