槲皮素对奈瑟球菌感染脑膜炎大鼠继发内毒素血症的抑制作用及机制研究

doi:10.12092/j.issn.1009-2501.2019.06.009

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (6): 658-664.doi: 10.12092/j.issn.1009-2501.2019.06.009

槲皮素对奈瑟球菌感染脑膜炎大鼠继发内毒素血症的抑制作用及机制研究

郦铮铮¹，陈瑾²，潘珍珍³，潘思培¹，张楠¹

¹温州医科大学附属第一医院神经内科，温州 325000，浙江；²台州市立医院儿内科，台州 318000，浙江；³温州医科大学附属第一医院感染科，温州 325000，浙江

收稿日期:2018-08-09 修回日期:2019-05-16 出版日期:2019-06-26 发布日期:2019-06-25
通讯作者: 张楠，女，硕士，主治医师，研究方向：神经内科。 E-mail：y197810lyy@163.com
作者简介:郦铮铮，女，硕士，主治医师，研究方向：神经内科。 Tel：13777780045 E-mail：y197810lyy@163.com
基金资助:
温州市科技计划项目（Y20170008）；浙江省科技厅专项课题（2016R86785）

Inhibitory effect and mechanism of quercetin on secondary endotoxemia in rats with Neisseria infection

LI Zhengzheng ¹, CHEN Jin², PAN Zhenzhen³, PAN Sipei¹, ZHANG Nan¹

¹ Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China; ²Department of Pediatrics, Taizhou Hospital, Taizhou 318000, Zhejiang, China; ³Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

Received:2018-08-09 Revised:2019-05-16 Online:2019-06-26 Published:2019-06-25

摘要/Abstract

摘要：

目的:分析槲皮素对奈瑟球菌感染脑膜炎大鼠继发内毒素血症的抑制作用影响。方法:选取SPF级Wistar雄性大鼠60只，随机数字表法将大鼠分成6组，分别是模型组、正常组、阳性对照组、低剂量槲皮素组、中剂量槲皮素组及高剂量槲皮素组，每组各10只，除正常组大鼠外，其他大鼠制备奈瑟球菌感染脑膜炎模型，造模后阳性对照组灌胃2 mL剂量为100 mg/L的地塞米松药液，低、中、高剂量槲皮素组灌胃2 mL剂量为50、100、200 mg/L的槲皮素药液，正常组与模型组大鼠灌胃等剂量生理盐水，各组大鼠给药间隔12 h，共给药5次。观察各组大鼠给药12、24、36、48及60 h时其存活率状况，同时间隔12 h检测大鼠体温一次，ELISA法检测血清IL-6、TNF-α、脂多糖、IL-1β、IL-8含量，Western blot检测p65与IκBα蛋白表达，RT-PCR检测脑组织Toll样受体4（TLR4）mRNA、CD68 mRNA相对表达量。结果:造模24 h内模型组大鼠全部死亡，模型组大鼠存活率低于正常组，中剂量及高剂量槲皮素组大鼠存活率优于模型组、阳性对照组及低剂量槲皮素组，差异有统计学意义（P＜0.05）；模型组大鼠血清IL-6、TNF-α、IL-1β及IL-8含量显著高于正常组（P＜0.05），其他各给药组血清IL-6、TNF-α、IL-1β及IL-8含量显著低于模型组。其中，中、高剂量槲皮素组大鼠降低显著，和模型组、阳性对照组对比差异有统计学意义（P＜0.05）。模型组大鼠IκBα蛋白表达比正常组下降，p65蛋白表达比正常组上升，中、高剂量槲皮素组大鼠IκBα蛋白表达比模型组、阳性对照组上升，p65蛋白比模型组、阳性对照组下降，差异均有统计学意义（P＜0.05）。结论:槲皮素可抑制奈瑟球菌感染脑膜炎大鼠机体NF-κB炎症通路，降低血清炎性因子含量，提高大鼠存活率。

关键词: 细菌性脑膜炎, 脑膜炎奈瑟球菌, 内毒素血症, 炎性因子, 槲皮素

Abstract:

AIM: To analyze the effect of quercetin on the inhibition of secondary endotoxemia in rats with Neisseria meningitis. METHODS: Sixty Wistar male rats of SPF grade were randomly divided into six groups: model group, normal group, positive control group, low dose quercetin group, medium dose quercetin group and high dose sputum. 10 rats in each group, except for the normal group, the other rats were prepared with Neisseria infection meningitis model. After the model was established, the positive control group was intragastrically administered with a 2 mL dose of 100 mg/L dexamethasone solution. Low-dose, medium-dose and high-dose quercetin groups were intragastrically administered with 2 mL doses of 50, 100, 200 mg/L quercetin solution, and normal group and model group rats were given equal doses of normal saline. Rats were administered at intervals of 12 h for a total of five doses. The survival rate of rats in each group was observed at 12, 24, 36, 48 and 60 hours. The body temperature of rats was measured once every 12 hours. Serum IL-6, TNF-α, lipopolysaccharide, IL-1β and IL-8 content were detected by ELISA. Western blot was used to detect the p65 and IκBα protein expression, RT-PCR was used to detect the relative expression of brain tissue Toll-like receptor 4 (TLR4) mRNA and CD68 mRNA. RESULTS:All the rats in the model group died within 24 hours after modeling, and the survival rate of the model group was lower than that of the normal group. The survival rate of the medium dose and high dose quercetin group was better than that of the model group, the positive control group and the low dose quercetin group. The difference was statistically significant (P<0.05). The serum levels of IL-6, TNF-α, IL-1β and IL-8 in the model group were significantly higher than those in the normal group (P<0.05). The levels of IL-6, TNF-α, IL-1β and IL-8 in the quercetin groups were significantly lower than those in the model group. Among them, the rats in the middle dose and high dose quercetin groups decreased significantly, and the differences between the model group and the positive control group were statistically significant (P<0.05). The expression of IκBα protein in the model group was lower than that in the normal group, and the expression of p65 protein was higher than that in the normal group. The expression of IκBα protein in the middle dose and high dose quercetin group was higher than that in the model group and the positive control group. The p65 protein in the middle dose and high dose quercetin group was lower than the model group and the positive control group, and the difference was statistically significant (P<0.05). CONCLUSION: Quercetin can inhibit the NF-κB inflammatory pathway in rats with Neisseria meningitis, reduce the content of serum inflammatory factors, and improve the survival rate of rats.

Key words: bacterial meningitis, Neisseria meningitidis, endotoxemia, inflammatory factors, quercetin

中图分类号:

郦铮铮，陈瑾，潘珍珍，潘思培，张楠. 槲皮素对奈瑟球菌感染脑膜炎大鼠继发内毒素血症的抑制作用及机制研究[J]. 中国临床药理学与治疗学, 2019, 24(6): 658-664.

LI Zhengzheng, CHEN Jin, PAN Zhenzhen, PAN Sipei, ZHANG Nan. Inhibitory effect and mechanism of quercetin on secondary endotoxemia in rats with Neisseria infection[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(6): 658-664.

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槲皮素对奈瑟球菌感染脑膜炎大鼠继发内毒素血症的抑制作用及机制研究

Inhibitory effect and mechanism of quercetin on secondary endotoxemia in rats with Neisseria infection

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