丙酸钠通过抑制NLRP3保护脓毒症大鼠的结肠组织

doi:10.3969/j.issn.2095-9400.2020.09.005

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摘要目的：探究丙酸钠（SP）对大鼠脓毒症模型结肠组织的保护作用并研究其与NLRP3炎性小体的关系。方法：采用盲肠结扎穿刺法建立脓毒症动物模型，随机分为假手术（Sham）组、模型（CLP）组、模型+SP（CLP+SP）组和假手术+SP（Sham+SP）组。建模24 h后处死各组大鼠，收集结肠组织。HE染色观察各组大鼠结肠结构变化，ELISA试剂盒检测结肠组织中IL-6、TGF-β和TNF-α含量，Western blot和免疫组化染色检测结肠紧密连接蛋白（claudin-1和occludin）和NLRP3炎性小体的表达情况。用同样的方法建立脓毒症模型，记录每组大鼠72 h生存率。结果：SP治疗能提高CLP组大鼠的生存率，减少病理损伤。CLP+SP组结肠组织中IL-6、TGF-β和TNF-α水平较CLP组低（P＜0.05）。相比CLP组，CLP+SP组结肠组织中claudin-1和occludin表达有所增加（P＜0.05）。CLP+SP组结肠组织中NLRP3、caspase-1、IL-β和IL-18表达与CLP组比较明显降低（P＜0.05）。结论：SP能提高脓毒症大鼠的存活率。此外，SP可能通过提高脓毒症大鼠结肠组织中紧密连接蛋白的表达，抑制NLRP3炎性小体的激活来减少结肠损伤。

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	谢献政
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关键词 ：丙酸钠, 紧密连接蛋白, NLRP3, 脓毒症, 大鼠

Abstract：Objective: To explore the protective effect of sodium propionate (SP) on colon tissue of septic rats and study its relationship with NLRP3 inflammasomes. Methods: Animal models of sepsis were established by cecum ligation and puncture (CLP) and randomly divided as sham operation group, model group, model+SP group and sham operation+SP group. Rats of each group were sacrificed 24 hours after modeling, and colonic tissues were collected. HE staining was used to observe the changes of colonic structure in each group of rats and ELISA kit to detect IL-6, TGF-β and TNF-α levels in colon tissue. Western blot and immunohistochemical staining were used to detect the expression of claudin-1 and occludin and NLRP3 inflammasomes. The same method was used to establish a sepsis model, and the 72 h survival rate of each group of rats was recorded. Results: SP treatment could improve the survival rate and reduce pathological damage in the model group. The levels of IL-6, TGF-β and TNF-α in colon tissue of model+SP group were lower than those of the model group. Compared with the model group, the expression of claudin-1 and occludin in the colon tissue of the model+SP group increased. The expressions of NLRP3, caspase-1, IL-β and IL-18 in colon tissue of model+SP group were significantly lower than those of the model group. Conclusion: SP can improve the survival rate of sepsis rats. In addition, SP reduces colon injury by increasing the expression of tight junction proteins in the colon tissue of sepsis rats and inhibiting the activation of NLRP3 inflammatory inflammasomes.

Key words： sodium propionate tight junction proteins NLRP3 inflammasomes sepsis rats

收稿日期: 2020-04-22

基金资助:浙江省大学生科技创新活动计划（2019R413079）。

通讯作者: 陈肖鸣，主任医师，教授，Email：cxm@wmu.edu.cn。

作者简介: 谢献政（1994-），男，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2020.09.005 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I9/712

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