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心阳片通过抑制NLRP3炎性小体保护慢性心力衰竭肾脏炎性损伤的作用及机制研究

Protective effects and mechanism of Xinyang tablet on renal inflammatory injury in chronic heart failure by inhibiting NLRP3 inflammasome

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【作者】 王俊岩王陵军梁碧容张璐冼绍祥汪朝晖

【Author】 WANG Jun-yan;WANG Ling-jun;LIANG Bi-rong;ZHANG Lu;XIAN Shao-xiang;WANG Zhao-hui;First Clinical College of Guangzhou University of Chinese Medicine;First Affiliated Hospital of Guangzhou University of Chinese Medicine;Lingnan Medical Research Center,Guangzhou University of Chinese Medicine;Key Laboratory of TCM Prevention and Treatment of CHF in Universities of Guangdong Province;Key Laboratory of TCM Prevention and Treatment of CHF in Guangzhou;

【通讯作者】 汪朝晖;

【机构】 广州中医药大学第一临床学院广州中医药大学第一附属医院广州中医药大学岭南医学研究中心广东省普通高校慢性心力衰竭中医药防治重点实验室广州市慢性心力衰竭中医药防治重点实验室

【摘要】 目的:观察慢性心力衰竭(CHF)对肾脏炎性损伤和纤维化影响及心阳片的干预作用。方法:随机将60只C57BL/6J小鼠分为假手术组、模型组、中药低、中、高剂量组、阳性对照组,通过主动脉缩窄术建立CHF模型小鼠,造模后中药低、中、高剂量组给予心阳片对应剂量灌胃,阳性对照组给予培哚普利灌胃,假手术组和模型组给予等量生理盐水灌胃,连续给药8周后,小动物超声检测小鼠心脏射血分数、收缩分数变化。于末次给药2 h后取材,Masson染色观察肾脏纤维化水平,免疫荧光法检测肾脏组织NLRP3蛋白表达水平,免疫组化法检测肾脏NLRP3、Caspase1、IL1β、NF-κB p65蛋白表达情况,RT-PCR法检测肾脏组织NF-κB、IL 1β、IL 18、IL 6、TNF-αmRNA表达水平。结果:与假手术组比较,模型组小鼠心脏EF、FS水平明显降低,肾脏纤维化水平明显升高,肾脏NLRP3、Caspase1、IL1β、NF-κB p65蛋白表达明显升高,NF-κB、IL 1β、IL 18、IL 6、TNF-αmRNA表达水平明显升高;与模型组比较,经治疗后各项指标水平明显改善,差异有统计学意义。结论:心阳片在改善CHF小鼠心功能的同时能够改善肾脏炎性损伤,抑制纤维化,其机制可能是通过调控NF-κB/NLRP3信号通路、抑制炎性反应实现的。

【Abstract】 Objective: To observe the effect of chronic heart failure on kidney inflammatory injury and fibrosis and the intervention effect of Xinyang Tablet. Methods: 60 C57 BL/6 J mice were randomly divided into sham operation group, model group, low, medium, high dose groups of traditional Chinese medicine and positive group. CHF model mice were established by aortic coarctation, after the model establishment, the low, medium and high doses of traditional Chinese medicine were given to the corresponding doses of Xinyang Tablet, the positive group was given perindopril. Sham operation group and model group were given the same amount of saline, after 8 weeks of continuous administration, the changes of ejection fraction and contraction fraction of the mice were detected by ultrasound,and after 2 hours of the last administration, the material was taken. The level of kidney fibrosis was observed by Masson staining, and the expression level of NLRP3 protein was detected by immunofluorescence. The expression of NLRP3、Caspase1、IL1β and NF-κB p65 proteins were detected by Immunohistochemistry, and the expression of NF-κB、IL 1β、IL 18、IL 6、TNF-α mRNA were detected by RT-PCR. Results: Compared with the sham operation group, the levels of EF and FS in the model group were significantly decreased. The level of kidney fibrosis was significantly increased, the expression of NLRP3, Caspase1, IL1β and NF-κB p65 proteins were significantly increased, and the expression levels of NF-κB, IL-1β, IL 18, IL 6 and TNF-α were significantly increased; After treatment, the levels of various indicators improved significantly, and the differences compared with the model group were statistically significant. Conclusion: Xinyang Pian can not only improve the cardiac function of CHF mice, but also improve kidney inflammatory injury and inhibit fibrosis, which its mechanism may be related to regulate NF-κB/NLRP3 signaling pathway and inhibits inflammatory response.

【基金】 国家自然科学基金资助项目(81673920,81673796,81973776,81973777)-基于AGEs-自噬-内皮细胞向间质细胞转化机制探讨益气温阳活血法防治心力衰竭心肌纤维化的作用,益气养阴活血法调节MLK/JNK-自噬机制介导的心脏成纤维细胞激活防治心力衰竭心肌纤维化的作用,基于HMGB1/RAGE-自噬调控巨噬细胞极化机制探讨益气温阳活血利水法防治心力衰竭心肌纤维化的作用,基于Mtln调控肌浆网-线粒体交互作用下的钙稳态探讨益气活血利水法防治心力衰竭的作用及机制;广东省自然科学基金重点项目(2017A030313454)-AGEs-RAGEPP2A轴介导的tau蛋白磷酸化在慢性心力衰竭认知障碍中的作用以及益气温阳活血法的干预
  • 【文献出处】 中国中医基础医学杂志 ,Journal of Basic Chinese Medicine , 编辑部邮箱 ,2021年01期
  • 【分类号】R285.5
  • 【被引频次】8
  • 【下载频次】333
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