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

Abstract

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.

Elucidating the Novel Mechanism of Ligustrazine in Preventing Postoperative Peritoneal Adhesion Formation

“…Loading capacity and entrapment efficiency are two pivotal indicators to measure the properties of nanoparticles. The PLA nanoparticles loaded with ligustrazine had high loading capacity and entrapment efficiency, as we reported previously [25]. It also had uniform spherical morphology with a smooth surface and good dispersivity (Figure 11(a)).…”

“…The distribution of particle size is about 200 nm. And LN had stable and sustained release behavior, evidenced by the in vitro drug release assay [ 25 ]. The outstanding features of LN are the prominently sustained release effect and good stability for tissue penetration via a positive targeting mechanism, which may be a novel agent for preventing PPA.…”

“…LN was prepared by our team as previously described [ 25 ]. A proper amount of ligustrazine was dissolved in 0.25% poloxamer solution to prepare 1 mg/ml ligustrazine solution, that is, LZ.…”

“…The distribution of particle size is about 200 nm. And LN had stable and sustained release behavior, evidenced by the in vitro drug release assay [25].…”

Development of Pharmacological Mechanism of Chinese Medicine Gastrodia Elata in the Treatment of Parkinson’s Disease

“…Activation of M1-type microglia is a common phenomenon [8], and their production of pro-inflammatory factors, such as TNF-α, IL-6, IL-12, and IL-1β, has the potential to cause damage to neuronal cells or even to trigger death, but at the same time, it also leads to an increase in the activity of the microglia that thereby triggering the development of PD, creating a continuous vicious cycle. One study found that the expression levels of TLR4, NF-Κb, p65, and p38MAPK were significantly increased in the brain of Parkinsonian rats [9]. The expression of these substances can be significantly reduced by using tensin, and furthermore, the expression and decline of these substances become greater with the increase of tensin dose.…”