ABSTRACT
Objective::To established the model of chronic alcoholic liver injury in rats by long-term(8 weeks) alcoholic gavage, to study the effects of Tibetan medicine Lagotis brachystachys extracts on Toll-like receptor(TLR)2/myeloid differentiation factor 88(MyD88)/nuclear factor kappa B (NF-κB)and NOD like receptor protein 3(NALP3) signaling pathways and study preliminary the mechanism of action of chronic alcoholic liver injury. Method::Sixty male Sprague-Dawley rats were randomly divided into normal group, model group, bifendate positive drug group (0.1 g·kg-1) and L. brachystachys low, medium and high-dose groups (0.5, 1, 2 g·kg-1), the corresponding drugs were given at 10 mL·kg-1 in each morning, and the 56 degree Liquor was administered by the afternoon gradient alcoholic gavage method.After 8 weeks, the levels of serum aspartate transaminase (AST), serum alanineaminotransfease(ALT), serum total cholesterol(TC), triglyceride(TG), interleukin-1β(IL-1β), and the liver levels of L-glutathione(GSH)were measured. The expression of TLR2, MyD88, NF-κB and NALP3 protein in liver were detected by Western blot.Hematoxylin-eosin (HE) staining was used to observe the pathological changes of liver tissue. Result::Compared with normal group, the serum levels of AST, ALT, TC, TG and IL-1β in model group were significantly increased (P<0.05, P<0.01). Compared with model group, the serum AST, ALT, TC, TG and IL-1β levels were decreased in the various doses of L. brachystachys, and the high dose group was particularly effective (P<0.05, P<0.01). Compared with normal group, the GSH level in the liver homogenate of model group decreased significantly, and the difference was not statistically significant. The levels of TLR2, MyD88, NF-κB and NALP3 in the liver tissue of model group were significantly increased (P<0.05, P<0.01). The GSH levels in the liver and the protein expression of TLR2, MyD88, NF-κB and NALP3 were decreased in L. brachystachys group (P<0.05, P<0.01). The liver pathological section showed that L. brachystachys can improve the pathological changes of rat liver tissue. Conclusion::L. brachystachys can protect liver from alcohol-induced chronic liver injury in rats. The mechanism was related to TLR2/MyD88/NF-κB and NALP3 signaling pathway.
ABSTRACT
Toll-like receptor (TLR)/MyD88/NF-KB signaling pathway is an important pathway in the body's inflammatory system. It is widely distributed in various tissue cells and participates in the regulation and regulation of various diseases, such as autoimmune diseases, inflammatory diseases, and infectious diseases, allergic diseases, etc. The TLR is a transmembrane protein that recognizes multiple types of pathogen-associated molecular patterns (such as lipopolysaccharide, sodium urate crystals, viral double-stranded RNA, etc.), causing an inflammatory immune response in body, and all TLRs are activated. The MyD88-dependent pathway thereby activates NF-κB, which ultimately leads to the release of inflammatory mediators and cytokines and acts as an anti-inflammatory immune regulator. At present, the research on TLR/MyD88/NF-κB signaling pathway is more in-depth, and has witnessed more progress. This article starts with the mechanism of action of TLR/MyD88/NF-κB signaling pathway in body and reviews its regulation in different diseases.