葡萄籽提取物对慢性牙周炎合并动脉粥样硬化大鼠氧化应激及主动脉病理变化的影响

doi:10.19439/j.sjos.2022.06.006

摘要/Abstract

摘要： 目的: 探讨葡萄籽提取物对慢性牙周炎合并动脉粥样硬化大鼠主动脉病理变化的影响,并分析可能的机制。方法: 将15只SPF级SD雄性成功建立慢性牙周炎合并动脉粥样硬化模型的大鼠随机分为模型组,葡萄籽提取物低、高剂量组,每组各5只,另取5只正常大鼠作为对照组。其中,葡萄籽提取物低、高剂量组大鼠分别给予葡萄籽提取物40、80 mg·kg^-1·d^-1灌胃处理（连续4周）,正常对照组及模型组大鼠同时间灌胃等量生理盐水。采用H-E染色并采集腹主动脉最大内-中膜厚度值（intima-media thickness, IMT）,采用比色法检测血清中超氧化物歧化酶（superoxide dismutase,SOD）活性、丙二醛（MDA）含量,采用酶联免疫吸附（ELISA）法检测血清谷胱甘肽（GSH-px）含量,采用ELISA法检测各组大鼠血清中肿瘤坏死因子（TNF-α）、白介素6（IL-6）水平,采用免疫印迹法检测主动脉组织中p38丝裂原激活蛋白激酶/核转录因子kappa B p65（p38MAPK/NF-κB p65）通路蛋白水平。采用SPSS 20.0软件包进行统计学分析。结果: 模型组大鼠腹主动脉血管内膜不规则增厚,有大量炎性细胞浸润,出现动脉血管病变。葡萄籽提取物低、高剂量组腹主动脉血管内膜斑块减少,炎性细胞明显减少,动脉血管病变有所改善;高剂量组比低剂量组改善更加明显。与对照组相比,模型组大鼠IMT、血清MDA、TNF-α、IL-6水平及p-p38MAPK/p38MAPK、NF-κB p65蛋白水平显著升高,血清SOD、GSH-px表达显著下调（P<0.05）。与模型组相比,葡萄籽提取物低、高剂量组大鼠IMT、血清MDA、TNF-α、IL-6及p-p38MAPK/p38MAPK、NF-κB p65蛋白水平显著降低,血清SOD、GSH-px水平显著升高（P<0.05）。结论: 葡萄籽提取物可抑制慢性牙周炎合并动脉粥样硬化大鼠血清氧化应激水平及炎症反应,进而改善主动脉血管内膜病变,可能通过抑制p38MAPK/NF-κB p65通路活化而实现。

关键词: 慢性牙周炎, 动脉粥样硬化, 葡萄籽提取物, 氧化应激, 主动脉病理变化

Abstract: PURPOSE: To investigate the effect of grape seed extract on pathological changes of aorta in rats with chronic periodontitis and arteriosclerosis, and to analyze the possible mechanism. METHODS: Fifteen SPF male rats with chronic periodontitis and arteriosclerosis were randomly divided into three groups, i.e., model group(n=5), low dose of grape seed extract group (n=5), high dose of grape seed extract group (n=5) , and control group (n=10). The rats in the low and high dose groups were treated with 40 mg·kg^-1·d^-1 and 80 mg·kg^-1·d^-1 for 4 weeks respectively, while the rats in the normal control group and the model group were treated with the same amount of normal saline at the same time. The maximal intima-media thickness(IMT) of abdominal aorta was measured by H-E staining, the activity of SOD and the content of MDA in serum were measured by colorimetry, the content of GSH-px in serum and serum levels of inflammatory factor (TNF-α) and interleukin-6(IL-6) were detected by ELISA. p38 mitogen-activated protein kinase/nuclear transcription factor Kappa B p65(p38 MAPK/NF-κB p65) pathway was detected by Western blotting. SPSS 20.0 software package was used for statistical analysis. RESULTS: In the model group, the intima of abdominal aorta was irregularly thickened, with a lot of inflammatory cell infiltration, and arterial lesions appeared. In the low-and high-dose groups of grape seed extract, the plaque of abdominal aorta intima decreased and inflammatory cells reduced significantly, arterial vascular disease was improved, and the improvement was more obvious in high dose group than in low dose group. Compared with the control group, the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and serum SOD and GSH-px in the model group were increased, while those in the model group were decreased(P<0.05); the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and SOD, GSH-px were decreased in the low and high dose groups(P<0.05). CONCLUSIONS: Grape seed extract can inhibit the oxidative stress level and inflammatory reaction in serum of chronic periodontitis with arteriosclerosis rats, thus improving the intimal lesion of aorta, possibly by inhibiting the activation of p38MAPK/NF-κB p65 pathway.

Key words: Chronic periodontitis, Arteriosclerosis, Grape seed extract, Oxidative stress, Pathological changes of aorta

中图分类号:

R781.4

许佳丽, 孙衎达, 朱雅琦. 葡萄籽提取物对慢性牙周炎合并动脉粥样硬化大鼠氧化应激及主动脉病理变化的影响[J]. 上海口腔医学, 2022, 31(6): 597-601.

XU Jia-li, SUN Kan-da, ZHU Ya-qi. Effect of grape seed extract on oxidative stress and pathological changes of aorta in rats with chronic periodontitis and arteriosclerosis[J]. Shanghai Journal of Stomatology, 2022, 31(6): 597-601.

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