天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (1): 32-37.doi: 10.11958/20181220

• 实验研究 • 上一篇    下一篇

嗜酸乳杆菌调节NO及其氧化介质对动脉粥样硬化模型大鼠的影响

王云鹏 1，郑文武 2，夏梦 2△，程玲 3，廖双华 1，李丹 1，陈雨露 1，李亚菲 1   

  1. 基金项目：西南医科大学附属医院院级基金（2017-PT-34） 作者单位：1西南医科大学临床医学院（邮编646000）；2西南医科大学附属医院心血管内科，3感染科 作者简介：王云鹏（1992），男，硕士研究生在读，主要从事心血管疾病方面研究 ?通讯作者 E-mail: 294544899@qq.com
  • 收稿日期:2018-08-15 修回日期:2018-11-27 出版日期:2019-01-15 发布日期:2019-01-15
  • 通讯作者: 夏梦 E-mail:294544899@qq.com
  • 基金资助:
    西南医科大学附属医院院级基金

Lactobacillus acidophilus regulates NO and its oxidative mediator in atherosclerosis model rats

WANG Yun-peng1, ZHENG Wen-wu2, XIA Meng2△, CHENG Ling3, LIAO Shuang-hua1, LI Dan1, CHEN Yu-lu1, LI Ya-fei1   

  1. 1 School of Southwest Medical University, Luzhou 646000, China; 2 Department of Cardiology, 3 Department of Infectious Diseases, the Affiliated Hospital of Southwest Medical University △Corresponding Author E-mail: 294544899@qq.com
  • Received:2018-08-15 Revised:2018-11-27 Published:2019-01-15 Online:2019-01-15

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摘要： 目的 研究嗜酸乳杆菌对一氧化氮（NO）及其氧化介质表达的影响，探讨嗜酸乳杆菌抗动脉粥样硬化的机 制。方法 24只SPF级雄性大鼠随机分为正常饮食组、高脂饮食组和嗜酸乳杆菌组，每组8只。正常饮食组大鼠以 普通饲料喂养，高脂饮食组以高脂饲料+腹腔注射维生素D3+免疫损伤法+FeSO4喂养建立动脉粥样硬化模型，嗜酸 乳杆菌组大鼠在高脂饮食组的基础上，每天灌胃0.5 mL嗜酸乳杆菌菌液（1×109 CFU/mL），实验第4、8、12周末称量动 物体质量。喂养 12 周后处死动物，检测血清氧化低密度脂蛋白（oxLDL）、NO、精氨酸、精氨酸酶、过氧亚硝基 （ONOO-）含量。分离大鼠主动脉血管，HE染色观察主动脉形态学变化，Real-time PCR检测eNOS、iNOS mRNA表达， Western blot 检测主动脉NF-κB p65亚基的表达。结果 （1）整个实验过程中，高脂饮食组和嗜酸乳杆菌组大鼠体质 量变化差异无统计学意义（P＞0.05），但较正常饮食组均有明显增长（P < 0.01）。（2）HE染色结果显示，高脂饮食大鼠 中主动脉形成广泛的动脉粥样硬化病变，嗜酸乳杆菌组大鼠的主动脉形态得到明显改善，仅内皮细胞增生，没有观 察到平滑肌细胞的坏死。（3）与正常饮食组相比，高脂饮食组大鼠血清oxLDL、ONOO-、精氨酸酶、主动脉iNOS mRNA 和细胞核NF-κB p65表达水平升高（P＜0.01），血清NO和精氨酸含量、主动脉eNOS mRNA 及胞质NF-κB p65亚基表 达水平降低（P＜0.01）；而嗜酸乳杆菌恰好能逆转上述改变（P＜0.01）。结论 嗜酸乳杆菌可能通过调节NOS的表 达、增加NO生物利用度、保护内皮功能来发挥抗动脉粥样硬化作用。

关键词: 嗜酸乳杆菌, 动脉粥样硬化, 动物实验, 一氧化氮, 转录因子RelA

Abstract: Objective To investigate the effect of lactobacillus acidophilus on the expression of nitric oxide (NO) and its oxidative mediators, and to explore the anti-atherosclerosis mechanism of lactobacillus acidophilus. Methods Twentyfour male SPF rats were randomly divided into normal diet group, high-fat diet group and lactobacillus acidophilus group, with 8 rats in each group. The rats in the normal diet group were fed with normal diet, and the high-fat diet group was fed with high-fat diet + intraperitoneal injection of vitamin D3 + immune injury + FeSO4 to establish an atherosclerosis model. The rats in the lactobacillus acidophilus group were intragastrically administered with 0.5 mL of lactobacillus acidophilus per day (1×109 CFU/mL) on the basis of the high-fat diet. Rats were weighed at the 4th, 8th and 12th weekends. After 12 weeks of feeding, the serum was taken from abdominal aorta to detect the contents of oxidized low density lipoprotein (oxLDL), NO, arginine, arginase, and peroxynitrite (ONOO-). The aorta was isolated to observe the morphological change by HE staining. The expressions of eNOS and iNOS mRNA were detected by Real-time PCR, and the expressions of NF-κB p65 subunits were detected by Western blot assay. Results (1) There was no significant difference in body weight between the high-fat diet group and the lactobacillus acidophilus group during the whole experiment (P＞0.05), but both were significantly increased compared with those of the normal diet group (P < 0.01). (2) HE staining showed that the aorta formed a wide range of atherosclerotic lesions in the high-fat diet rats, and the aortic morphology was significantly improved in the lactobacillus acidophilus group. Only endothelial cell proliferation was found, and no smooth muscle cell necrosis was observed in this group. (3) Compared with normal diet group, the serum expressions of oxLDL, ONOO- , arginase, aortic iNOS mRNA and nuclear NF-κB p65 were increased in high-fat diet group (P＜0.01), and the serum arginine content and aortic eNOS mRNA expression levels were decreased (P＜0.01). While lactobacillus acidophilus can just reverse the above changes (P＜0.01). Conclusion Lactobacillus acidophilus may exert anti-atherosclerotic effects by regulating the expression of NOS, increasing NO bioavailability, and protecting endothelial function.

Key words: lactobacillus acidophilus, atherosclerosis, animal experimentation, nitric oxide, transcription factor RelA