Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion
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.
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.
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.
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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Posted 27 May, 2020
On 17 Jan, 2021
Received 28 Dec, 2020
Received 20 Dec, 2020
On 19 Dec, 2020
On 19 Dec, 2020
On 19 Dec, 2020
Received 04 Dec, 2020
Received 04 Dec, 2020
On 03 Dec, 2020
Invitations sent on 23 Jun, 2020
On 23 Jun, 2020
On 15 May, 2020
On 14 May, 2020
On 14 May, 2020
On 13 May, 2020
Effect of Ligustrazine Nanoparticles on Th1/Th2 Balance by TLR4/MyD88/NF-κB Pathway in Rats with Postoperative Peritoneal Adhesion
Posted 27 May, 2020
On 17 Jan, 2021
Received 28 Dec, 2020
Received 20 Dec, 2020
On 19 Dec, 2020
On 19 Dec, 2020
On 19 Dec, 2020
Received 04 Dec, 2020
Received 04 Dec, 2020
On 03 Dec, 2020
Invitations sent on 23 Jun, 2020
On 23 Jun, 2020
On 15 May, 2020
On 14 May, 2020
On 14 May, 2020
On 13 May, 2020
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.
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.
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.
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