This preprint is under consideration at BMC Surgery. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion
Yaoyao Bian
Nanjing University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9968-2501
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
Postoperative peritoneal adhesion, ligustrazine nanoparticle, Th1/Th2 balance, TLR4/MyD88/NF-κB pathway
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 27 May, 2020
No community comments so far
Editorial decision: Major revision
On 17 Jan, 2021
Review #4 received
Received 28 Dec, 2020
Review #3 received
Received 20 Dec, 2020
Reviewer #4 agreed
On 19 Dec, 2020
Reviewer #5 agreed
On 19 Dec, 2020
Reviewer #3 agreed
On 19 Dec, 2020
Review #1 received
Received 04 Dec, 2020
Review #2 received
Received 04 Dec, 2020
Reviewer #2 agreed
On 03 Dec, 2020
Reviewers invited
Invitations sent on 23 Jun, 2020
Reviewer #1 agreed
On 23 Jun, 2020
Editor assigned
On 15 May, 2020
Submission checks complete
On 14 May, 2020
Editor invited
On 14 May, 2020
First submitted
On 13 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This preprint is under consideration at BMC Surgery. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion
Yaoyao Bian
Nanjing University of Chinese Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-9968-2501
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 27 May, 2020
No community comments so far
Editorial decision: Major revision
On 17 Jan, 2021
Review #4 received
Received 28 Dec, 2020
Review #3 received
Received 20 Dec, 2020
Reviewer #4 agreed
On 19 Dec, 2020
Reviewer #5 agreed
On 19 Dec, 2020
Reviewer #3 agreed
On 19 Dec, 2020
Review #1 received
Received 04 Dec, 2020
Review #2 received
Received 04 Dec, 2020
Reviewer #2 agreed
On 03 Dec, 2020
Reviewers invited
Invitations sent on 23 Jun, 2020
Reviewer #1 agreed
On 23 Jun, 2020
Editor assigned
On 15 May, 2020
Submission checks complete
On 14 May, 2020
Editor invited
On 14 May, 2020
First submitted
On 13 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Figure 1
Figure 2
Figure 3
Figure 4