连翘苷调节NLRP3炎性通路对急性胸膜炎大鼠肺损伤的影响

doi:10.11958/20230399

天津医药 ›› 2024, Vol. 52 ›› Issue (2): 161-166.doi: 10.11958/20230399

连翘苷调节NLRP3炎性通路对急性胸膜炎大鼠肺损伤的影响

郝建玲¹(), 信婧婧², 王靖³, 田红³, 苏海涛⁴^,^△()

1.青岛市胸科医院门诊部（邮编266043）,2.发热门诊,3.综合内科,4.胸一科

收稿日期:2023-03-21 修回日期:2023-05-18 出版日期:2024-02-15 发布日期:2024-01-26
通讯作者: ^△ E-mail：jiangrfp5@163.com
作者简介:郝建玲（1972），女，副主任医师，主要从事呼吸、肺结核疾病方面研究。E-mail：t7m3m5q@163.com
基金资助:
青岛市中医药科技项目(2022-zyym25)

Effect of phillyrin regulating NLRP3 inflammatory pathway on exudates and lung injury in rats with acute pleurisy

HAO Jianling¹(), XIN Jingjing², WANG Jing³, TIAN Hong³, SU Haitao⁴^,^△()

1. Department of Outpatient, 2. Department of Fever Clinic, 3. Department of General Medicine, 4. Department of Chest 1, Qingdao Chest Hospital, Qingdao 266043, China

Received:2023-03-21 Revised:2023-05-18 Published:2024-02-15 Online:2024-01-26
Contact: ^△ E-mail: jiangrfp5@163.com

郝建玲, 信婧婧, 王靖, 田红, 苏海涛. 连翘苷调节NLRP3炎性通路对急性胸膜炎大鼠肺损伤的影响[J]. 天津医药, 2024, 52(2): 161-166.

HAO Jianling, XIN Jingjing, WANG Jing, TIAN Hong, SU Haitao. Effect of phillyrin regulating NLRP3 inflammatory pathway on exudates and lung injury in rats with acute pleurisy[J]. Tianjin Medical Journal, 2024, 52(2): 161-166.

摘要/Abstract

摘要：

目的探讨连翘苷通过调节NOD样受体热蛋白结构域相关蛋白3（NLRP3）炎性通路对急性胸膜炎大鼠渗出液和肺损伤的影响。方法将90只大鼠采用随机数字表法均分为对照组、模型组、连翘苷低剂量（PH-L，5 mg/kg）组、连翘苷中剂量（PH-M，10 mg/kg）组、连翘苷高剂量（PH- H，20 mg/kg）组及NLRP3通路抑制剂（PJ34，10 mg/kg）组。肺功能分析仪检测大鼠用力肺活量（FVC）、第0.1秒用力呼气量（FEV 0.1）、第0.3秒用力呼气量（FEV 0.3）；电子天平称量胸腔渗出物质量；瑞氏染色检测渗出物白细胞数；酶联免疫吸附试验检测渗出液中前列腺素E2（PGE2）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）含量；全自动血气分析仪检测大鼠动脉CO₂分压[p（CO₂）]、动脉氧分压[p（O₂）]；HE染色观察肺组织病理学变化；免疫组织化学染色检测NOD样受体热蛋白结构域相关蛋白3（NLRP3）、胱天蛋白酶1（Caspase-1）蛋白表达；Western blot检测NLRP3通路蛋白表达。结果与对照组比较，模型组大鼠胸腔渗出物质量和白细胞数、渗出液PGE2、MCP-1、IL-6、TNF-α含量、p（CO₂）、NLRP3通路蛋白表达增加，FVC、FEV 0.1、FEV 0.3、p（O₂）降低，肺组织出现明显的病理损伤（P<0.05）；与模型组比较，PH各组和PJ34组大鼠胸腔渗出物质量、白细胞数、渗出液PGE2、MCP-1、IL-6、TNF-α含量、p（CO₂）、NLRP3通路蛋白表达降低，FVC、FEV 0.1、FEV 0.3、p（O₂）增加，肺组织病理损伤好转（P<0.05）；与PH-H组比较，PJ34组上述指标差异无统计学意义（P>0.05）。结论 PH可通过抑制NLRP3通路激活，抑制炎症反应，改善急性胸膜炎引起的肺损伤。

关键词: 胸膜炎, 急性病, 连翘苷, 肺损伤, NLR家族, 热蛋白结构域包含蛋白3

Abstract:

Objective To investigate the impacts of phillyrin on exudates and lung injury in rats with acute pleurisy by regulating the NLRP3 inflammatory pathway. Methods Ninety rats were randomly divided into the control group, the model group, the low-dose phillyrin (PH-L, 5 mg/kg) group, the medium-dose phillyrin (PH-M, 10 mg/kg) group, the high-dose phillyrin (PH-H, 20 mg/kg) group and the NLRP3 pathway inhibitor (PJ34, 10 mg/kg) group. FVC, FEV 0.1 and FEV 0.3 were detected by lung function analyzer. Electronic balance was used to weigh the mass of chest exudate. The number of white blood cells in exudate was detected by Wright staining. Contents of prostaglandin E2 (PGE2), monocyte chemoattractant protein-1 (MCP-1), interleukin (IL) -6 and tumor necrosis factor-α (TNF-α) in exudate were detected by ELISA. Automatic blood gas analyzer was used to detect p (CO₂) and p (O₂) of rats. HE staining was used to observe pathological changes of lung tissue. The expression levels of NLRP3 and Caspase-1 protein were detected by immunohistochemistry. Western blot assay was used to detect the expression of NLRP3 pathway protein. Results Compared with the control group, the quality of pleural exudate and the number of white blood cells, the contents of PGE2, MCP-1, IL-6, TNF-α, the expression of p (CO₂) and NLRP3 pathway proteins in exudate of the model group increased obviously, FVC, FEV 0.1, FEV 0.3 and p (O₂) decreased obviously, and the lung tissue showed obvious pathological damage (P<0.05). Compared with the model group, the quality of pleural exudate and the number of white blood cells, the contents of PGE2, MCP-1, IL-6, TNF-α, the expression of p (CO₂), NLRP3 pathway proteins in the exudate of rats decreased obviously in the PH group and the PJ34 group, FVC, FEV 0.1, FEV 0.3 and p (O₂) increased obviously, the pathological injury of lung tissue was obviously improved (P<0.05). Compared with the PH-H group, there were no significant differences in the above indexes in the PJ34 group (P>0.05). Conclusion PH can improve lung injury induced by acute pleurisy in rats by inhibiting the activation of NLRP3 pathway and inhibiting inflammatory reaction.

Key words: pleurisy, acute disease, phillyrin, lung injury, NLR family, pyrin domain-containing 3 protein

中图分类号:

R285.5，R561.1

图/表 9

参考文献 21

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组别	FVC	FEV 0.1	FEV 0.3
对照组	18.59±2.13	4.88±0.32	15.14±2.30
模型组	10.12±2.01^a	1.21±0.14^a	6.22±2.25^a
PH-L组	13.55±2.30^b	2.55±0.13^b	9.13±2.10^b
PH-M组	16.40±2.10^bc	3.69±0.17^bc	11.68±1.77^bc
PH-H组	19.32±2.25^bcd	4.72±0.15^bcd	14.58±1.62^bcd
PJ34组	18.65±2.14^b	4.81±0.12^b	14.35±1.84^b
F	42.180^＊＊	982.071^＊＊	47.927^＊＊

组别	FVC	FEV 0.1	FEV 0.3
对照组	18.59±2.13	4.88±0.32	15.14±2.30
模型组	10.12±2.01^a	1.21±0.14^a	6.22±2.25^a
PH-L组	13.55±2.30^b	2.55±0.13^b	9.13±2.10^b
PH-M组	16.40±2.10^bc	3.69±0.17^bc	11.68±1.77^bc
PH-H组	19.32±2.25^bcd	4.72±0.15^bcd	14.58±1.62^bcd
PJ34组	18.65±2.14^b	4.81±0.12^b	14.35±1.84^b
F	42.180^＊＊	982.071^＊＊	47.927^＊＊

组别	渗出物质量/mg	白细胞数/（×10⁶/mL）
对照组	2.23±0.15	7.05±1.02
模型组	3.85±0.44^a	55.70±6.82^a
PH-L组	3.42±0.35^b	49.03±4.31^b
PH-M组	2.84±0.41^bc	44.20±5.01^b
PH-H组	2.55±0.36^bc	37.01±4.71^bcd
PJ34组	2.50±0.42^b	32.05±5.14^b
F	42.257^＊＊	188.739^＊＊

组别	渗出物质量/mg	白细胞数/（×10⁶/mL）
对照组	2.23±0.15	7.05±1.02
模型组	3.85±0.44^a	55.70±6.82^a
PH-L组	3.42±0.35^b	49.03±4.31^b
PH-M组	2.84±0.41^bc	44.20±5.01^b
PH-H组	2.55±0.36^bc	37.01±4.71^bcd
PJ34组	2.50±0.42^b	32.05±5.14^b
F	42.257^＊＊	188.739^＊＊

组别	PGE2/（ng/L）	MCP-1/（μg/L）	IL-6/（ng/L）	TNF-α/（ng/L）
对照组	405.01±22.03	52.03±5.14	140.30±7.42	352.14±16.21
模型组	676.25±45.32^a	145.70±18.35^a	186.02±11.34^a	460.35±21.41^a
PH-L组	601.14±33.54^b	115.36±16.72^b	170.02±10.41^b	432.54±19.02^b
PH-M组	538.02±28.56^bc	64.20±12.04^bc	161.21±10.35^b	410.14±13.46^bc
PH-H组	513.40±30.36^bc	56.01±13.03^bc	150.32±8.74^bcd	362.14±15.74^bcd
PJ34组	486.72±28.71^b	58.36±12.74^b	146.41±7.15^b	365.01±12.43^b
F	127.246^＊＊	122.490^＊＊	49.214^＊＊	104.780^＊＊

连翘苷调节NLRP3炎性通路对急性胸膜炎大鼠肺损伤的影响

Effect of phillyrin regulating NLRP3 inflammatory pathway on exudates and lung injury in rats with acute pleurisy

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参考文献 21

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组别	p（O₂）	p（CO₂）
对照组	8.68±0.92	4.54±0.55
模型组	4.07±0.75^a	8.43±1.01^a
PH-L组	5.31±0.63^b	7.22±0.62^b
PH-M组	6.10±0.55^b	5.72±0.77^bc
PH-H组	7.42±0.85^bcd	4.75±0.61^bcd
PJ34组	7.32±0.73^b	5.20±0.82^b
F	73.583^＊＊	63.523^＊＊

组别	NLRP3	Caspase-1
对照组	2.02±0.13	1.04±0.03
模型组	5.34±0.20^a	7.22±0.16^a
PH-L组	4.40±0.14^b	6.10±0.15^b
PH-M组	3.36±0.16^bc	5.02±0.12^bc
PH-H组	2.23±0.12^bcd	3.89±0.10^bcd
PJ34组	2.15±0.10^b	3.75±0.12^b
F	448.980^＊＊	1 580.975^＊＊

组别	p-NF-kB p65/ NF-kB p65	ASC	NLRP3	C-Caspase-1/ Caspase-1
对照组	0.30±0.02	0.35±0.03	0.25±0.03	0.30±0.04
模型组	0.93±0.08^a	0.90±0.08^a	0.88±0.07^a	0.92±0.10^a
PH-L组	0.75±0.09^b	0.77±0.08^b	0.66±0.05^b	0.75±0.10^b
PH-M组	0.54±0.05^bc	0.63±0.05^bc	0.42±0.05^bc	0.60±0.08^bc
PH-H组	0.41±0.06^bcd	0.38±0.04^bcd	0.30±0.06^bcd	0.39±0.05^bcd
PJ34组	0.37±0.04^b	0.42±0.06^b	0.32±0.05^b	0.41±0.06^b
F	76.814^＊＊	72.715^＊＊	108.811^＊＊	50.372^＊＊

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