HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR-<i>γ</i> Signalling Pathway

Zhao, Min; Bian, Yaoyao; Yang, Lili; Chen, Yanqi; Wang, Yajie; Ma, Yanting; Pei, Yuqiong; Li, Wenlin; Zeng, Li

doi:10.1155/2019/1769374

Cited by 35 publications

(23 citation statements)

References 62 publications

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“…Since this is the first study to validate that Sart1 can modulate macrophage polarization, we attempted to unmask the underlying mechanism. Previous studies have demonstrated that the STAT6/PPAR-γ signaling pathway is essential for macrophage polarization 32 , 36 . Therefore, the expression levels of p-STAT6 and PPAR-γ were evaluated in gain and loss-of-function assays.…”

Section: Discussionmentioning

confidence: 99%

Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis

et al. 2021

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Idiopathic pulmonary fibrosis (IPF) is a chronic and diffuse form of interstitial lung disease of unknown etiology with a fatal outcome. Although various strategies for IPF have been developed over the last few decades, no significant positive impact on the prognosis of IPF has been observed. According to the current paradigm, macrophages have been recognized to play a significant role in IPF pathogenesis. Here, we report a potential nanomedicine-based gene therapy for IPF based on regulate macrophage polarization. Method: C57BL/6 mice were obtained and used to establish a bleomycin (BLM)-induced pulmonary fibrosis animal model, and Sart1 siRNA-loaded liposomes were designed for in vivo experiment. The experimental animals were administered BLM intratracheally on day 0 and treated with Sart1 siRNA on days 14 and 17. In the in vitro experiment, we further examined the function of Sart1 in macrophages. Results: Our data indicated that the liposomes could passively target the fibrotic area in the lung and efficiently accumulate in macrophages. The suppression of Sart1 by siRNA-loaded liposomes significantly protected mice against BLM-induced lung injury and fibrosis, which was attributed to attenuated M2 macrophage infiltration in the lung. Conclusion: Our study provides a valuable reference for modulating macrophage polarization and a promising strategy for the treatment of pulmonary fibrosis in clinical settings.

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Section: Discussionmentioning

confidence: 99%

Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis

et al. 2021

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“…The PPA model was prepared as previous study reported [26] [27] . In brief, all rats were fasted for 12 h but allowed to drink water before the experiment.…”

Section: Animal Model Preparation and Group Assignmentmentioning

confidence: 99%

Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion

Yang

Lian

Zhang³

et al. 2020

Preprint

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Background Postoperative peritoneal adhesion (PPA) is regarded as fibrous bands connecting both injured abdominal wall and organs or adjacent tissues and associated with T helper (Th)1 and Th2 differentiation. However, the critical role of immunopathogenesis of adhesion formation was precisely unknown. Previously we demonstrated that ligustrazine have positive effects on adhesion formation. And microarray analysis revealed TLR4/MyD88/NF-κB pathway as an important underlying regulatory mechanism in the onset and development of PPA. To further explore the possible mechanism of PPA and enhance the specificity of ligustrazine delivery to injured sites of rodent models, a new agent polylactic acid (PLA) nanoparticles loaded with ligustrazine, that is, ligustrazine nanoparticles (LN) were applied. Methods Twenty-four SD rats were randomly divided into sham, model, LN and sodium hyaluronate (SH) groups. The structure of LN, including entrapment efficiency (EE) and loading capacity (LC), and in vitro drug release were calculated. Adhesions were scored and the masson’s trichrome staining was used to determine the collagen deposition. The expression of TLR4, MyD88 and NF-κB were measured by qPCR, Immunohistochemistry and western blot assay. Moreover, Th1-related cytokines (IFN-γ, IL-12), Th2-related cytokines (IL-4, IL-6) in the cecum tissue and serum were conducted by ELISA. Results LN had good EE, LC and control-release delivery characters with fairly uniform diameter and spherical morphology. It could effectively prevent adhesion formation after surgery. Besides, it could reduce collagen fibers accumulation, downregulate the expression levels of TLR4, MyD88 and NF-κB, and maintain Th1/Th2 balance. Conclusions Ligustrazine nanoparticles had effective effects on Th1/Th2 balance by regualtingTLR4/MyD88/NF-κB pathway in PPA rats. It may be served as a promising therapy on postoperative adhesion formation.

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“…The degree of adhesion was determined using a five-stage adhesion score system [ 13 , 24 , 25 ] by two independent investigators in a blinded way. This scoring system included five stages adhesion scores ranging from 0 to 4.…”

Section: Methodsmentioning

confidence: 99%

Effect of ligustrazine nanoparticles on Th1/Th2 balance by TLR4/MyD88/NF-κB pathway in rats with postoperative peritoneal adhesion

Yang

Lian

Zhang³

et al. 2021

BMC Surg

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Background Postoperative peritoneal adhesion (PPA) is regarded as fibrous bands connecting both injured abdominal wall and organs or adjacent tissues. It is associated with T helper (Th)1 and Th2 differentiation. However, the critical role of the immunopathogenesis of adhesion formation was precisely unknown. The aim of this study was to investigate the effect of a new agent polylactic acid (PLA) nanoparticles loaded with ligustrazine, that is, ligustrazine nanoparticles (LN) on PPA and identify the potential mechanism. Methods Twenty-four Sprague–Dawley rats were randomly divided into the sham, model, LN, and sodium hyaluronate (SH) groups. The structure of LN, including entrapment efficiency (EE) and loading capacity (LC), and in vitro drug release were calculated. Adhesions were scored and the Masson's trichrome staining was used to determine the collagen deposition. The expressions of TLR4, MyD88, and NF-κB were measured by qRT-PCR, immunohistochemistry, and western blot assay. Moreover, Th1-related cytokines (IFN-γ, IL-12), Th2-related cytokines (IL-4, IL-6) in the cecum tissue and serum were conducted by ELISA. Results LN had good EE, LC, and control-release delivery characters with fairly uniform diameter and spherical morphology. It could effectively prevent adhesion formation after surgery. Besides, it could reduce collagen fibers accumulation, downregulate the expression levels of TLR4, MyD88, and NF-κB, and maintain Th1/Th2 balance. Conclusions Ligustrazine nanoparticles had effective effects on Th1/Th2 balance by regulating TLR4/MyD88/NF-κB pathway in PPA rats. It may be served as a promising therapy on postoperative adhesion formation.

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HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR-γ Signalling Pathway

Cited by 35 publications

References 62 publications

Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis

Suppressing Sart1 to modulate macrophage polarization by siRNA-loaded liposomes: a promising therapeutic strategy for pulmonary fibrosis

Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion

Effect of ligustrazine nanoparticles on Th1/Th2 balance by TLR4/MyD88/NF-κB pathway in rats with postoperative peritoneal adhesion

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