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

doi:10.11958/20230399

Abstract

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

CLC Number:

R285.5，R561.1

Figures/Tables 9

References 21

[1]	ALIKHANI A, ABBASPOUR KASGARI H, MAJIDI H, et al. Brucella pleurisy:an extremely rare complication of brucellosis[J]. Clin Case Rep, 2022, 10(9):e6366-e6370. doi:10.1002/ccr3.6366.
[2]	BROWN S E, BYCROFT K A, ADAM K, et al. Acute fibrinous pleuropneumonia and septicaemia caused by Bibersteinia trehalosi in neonatal calves in New Zealand[J]. N Z Vet J, 2021, 69(1):51-57. doi:10.1080/00480169.2020.1792372.
[3]	HOU T, YANG M, YAN K, et al. Amentoflavone ameliorates carrageenan-induced pleurisy and lung injury by inhibiting the NF-κB/STAT3 pathways via Nrf2 activation[J]. Front Pharmacol, 2022, 13:763608. doi:10.3389/fphar.2022.763608.
[4]	XU J, NÚÑEZ G. The NLRP3 inflammasome: activation and regulation[J]. Trends Biochem Sci, 2023, 48(4):331-344. doi:10.1016/j.tibs.2022.10.002.
[5]	CHEN S, ZHANG S, WU H, et al. Protective effect of phillyrin against cerebral ischemia/reperfusion injury in rats and oxidative stress-induced cell apoptosis and autophagy in neurons[J]. Bioengineered, 2022, 13(3):7940-7950. doi:10.1080/21655979.2022.2042142.
[6]	TANG K, ZHONG B, LUO Q, et al. Phillyrin attenuates norepinephrine-induced cardiac hypertrophy and inflammatory response by suppressing p38/ERK1/2 MAPK and AKT/NF-kappaB pathways[J]. Eur J Pharmacol, 2022, 927:175022. doi:10.1016/j.ejphar.2022.175022.
[7]	MESSAOUD-NACER Y, CULERIER E, ROSE S, et al. STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS)[J]. Cell Death Dis, 2022, 13(3):269. doi:10.1038/s41419-022-04664-5.
[8]	LI Y, CHANG N, HAN Y, et al. Anti-inflammatory effects of Shufengjiedu capsule for upper respiratory infection via the ERK pathway[J]. Biomed Pharmacother, 2017, 94(1):758-766. doi:10.1016/j.biopha.2017.07.118.
[9]	ZHONG W T, WU Y C, XIE X X, et al. Phillyrin attenuates LPS-induced pulmonary inflammation via suppression of MAPK and NF-κB activation in acute lung injury mice[J]. Fitoterapia, 2013, 90(1):132-139. doi:10.1016/j.fitote.2013.06.003.
[10]	曹乐, 唐雅雯, 冯平, 等. 辛伐他汀对蛛网膜下腔出血早期脑损伤大鼠NLRP3炎性小体的表达及NF-κB信号通路的影响[J]. 脑与神经疾病杂志, 2023, 31(1):23-28.
	CAO L, TANG Y W, FENG P, et al. Effect of Simvastatin on the expression of NLRP3 inflammasome and NF-κB signaling pathway in rats with early subarachnoid hemorrhage[J]. Journal of Brain and Neurological Diseases, 2023, 31(1):23-28.
[11]	赵博, 杨馨怡, 屈新亮, 等. 黄芩茎叶抑制TRPV1通路改善大鼠急性胸膜炎的研究[J]. 中药药理与临床, 2022, 38(4):112-116.
	ZHAO B, YANG X Y, QU X L, et al. Effect of stem and leaf of Scutellaria baicalensis on acute pleurisy in rats by inhibiting TRPV1 pathway[J]. Pharmacology and Clinic of Chinese Traditional Medicine, 2022, 38(4):112-116. doi:10.13412/j.cnki.zyyl.20220418.002.
[12]	CAIAZZO E, MORELLO S, CARNUCCIO R, et al. The Ecto-5'-nucleotidase/CD73 inhibitor,α,β-methylene adenosine 5'-diphosphate,exacerbates carrageenan-induced pleurisy in rat[J]. Front Pharmacol, 2019, 10(1):775-784. doi:10.3389/fphar.2019.00775.
[13]	WANG G, ZHANG Y, HU N, et al. Mesenchymal stem cells attenuate acute lung injury in mice partly by suppressing alveolar macrophage activation in a PGE2-dependent manner[J]. Inflammation, 2022, 45(5):2000-2015. doi:10.1007/s10753-022-01670-9.
[14]	ZHAO H, CHEN H, XIAOYIN M, et al. Autophagy activation improves lung injury and inflammation in sepsis[J]. Inflammation, 2019, 42(2):426-439. doi:10.1007/s10753-018-00952-5.
[15]	黄媛恒, 陈健, 黄仁彬, 等. 玉郎伞提取物对模型大鼠胸膜炎TNF-α、PGE₂、NO的影响[J]. 中国药房, 2010, 21(3):200-202.
	HUANG Y H, CHEN J, HUANG R B, et al. Effect of Yulang Parasol extract on TNF-α,PGE₂ and NO in pleurisy of model rats[J]. Chinese Pharmacy, 2010, 21(3):200-202.
[16]	LANSLEY S M, CHEAH H M, LEE Y C. Role of MCP-1 in pleural effusion development in a carrageenan-induced murine model of pleurisy[J]. Respirology, 2017, 22(4):758-763. doi:10.1111/resp.12951.
[17]	HUANG Y, XU W, ZHOU R. NLRP3 inflammasome activation and cell death[J]. Cell Mol Immunol, 2021, 18(9):2114-2127. doi:10.1038/s41423-021-00740-6.
[18]	HSU C G, CHÁVEZ C L, ZHANG C, et al. The lipid peroxidation product 4-hydroxynonenal inhibits NLRP3 inflammasome activation and macrophage pyroptosis[J]. Cell Death Differ, 2022, 29(9):1790-1803. doi:10.1038/s41418-022-00966-5.
[19]	卓玉珍, 杨磊, 鹿燕敏, 等. 凉血活血方通过抑制NLRP3炎性小体活化保护脓毒症急性肺损伤小鼠的实验研究[J]. 中国中西医结合外科杂志, 2022, 28(2):173-178.
	ZHUO Y Z, YANG L, LU Y M, et al. Experimental study of Liangxue Huoxue Decoction ameliorates sepsis-induced ali in mice by inhibiting NLRP3 inflammasome[J]. Chinese Journal of Surgery of Integrated Traditional and Western Medicine, 2022, 28(2):173-178. doi:10.3969/j.issn.1007-6948.2022.02.005.
[20]	CAI B, ZHAO J, ZHANG Y, et al. USP5 attenuates NLRP3 inflammasome activation by promoting autophagic degradation of NLRP3[J]. Autophagy, 2022, 18(5):990-1004. doi:10.1080/15548627.2021.1965426.
[21]	ZHANG C, WANG X, WANG C, et al. Qingwenzhike prescription alleviates acute lung injury induced by LPS via inhibiting TLR4/NF-kB pathway and NLRP3 inflammasome activation[J]. Front Pharmacol, 2021, 12:790072. doi:10.3389/fphar.2021.790072.

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^＊＊