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Objective To investigate the effect of NOD-like receptor family pyrin domain containing 3（NLRP3) knockdown on a mouse model of nonalcoholic steatohepatitis (NASH) induced by high-fat high-carbohydrate (HFHC) diet. Methods A total of 44 mice were randomly divided into normal diet group (CON group) with 20 mice and HFHC group with 24 mice. At the end of week 14 of modeling，4 mice were randomly selected from the HFHC group for the pre-experiment of adeno-associated virus (AAV) by tail vein injection, and NLRP3 knockdown was verified after 4 weeks. After NLRP3 knockdown was verified at the end of week 18, the remaining 40 mice were given a single tail vein injection of AAV, and then they were divided into CON+NLRP3 knockdown negative control group (CON+NLRP3-NC group), CON+NLRP3 knockdown group (CON+NLRP3-KD group), HFHC+NLRP3- NC group, and HFHC+NLRP3-KD group, with 10 mice in each group. At the end of week 24, the activation of NLRP3 inflammasome was observed； related indicators were measured, including body weight, liver weight, liver index, and glucose metabolism (fasting blood glucose, fasting insulin, and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] index)；the indicators of liver lipid content (liver triglyceride [TG] and oil red O staining), liver inflammation (serum alanine aminotransferase [ALT] activity, HE staining, and inflammation-related genes), and liver fibrosis (Sirius Red staining and fibrosis-related genes) were measured. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the CON+NLRP3-NC group based on the results of Western Blot, the HFHC+NLRP3-NC group had significant increases in the protein expression levels of NLRP3, pro-Caspase1, Caspase1, ASC, and IL-1β, while the HFHC+NLRP3-KD group had significant reductions in these levels (all P<0.05). The HFHC+NLRP3-NC group showed varying degrees of increase in body weight, liver weight, liver index, and glucose metabolism indicators, while the HFHC+NLRP3-KD group showed significant improvements in these indicators (all P<0.05). As for hepatic fat deposition, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had a significant increase in liver TG, with a large number of red lipid droplets shown by oil red O staining, and the HFHC+ NLRP3-KD group had significant reductions in liver TG and the number of lipid droplets in the liver (all P<0.01). In terms of liver inflammation, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had significant increases in serum ALT, NAFLD activity score, and inflammation-related genes, while the HFHC+NLRP3-KD group had significant reductions in these indicators (all P<0.01). As for liver fibrosis, compared with the CON+NLRP3-NC group, the HFHC+NLRP3-NC group had significant increases in collagen fiber area and fibrosis-related genes, and the HFHC+NLRP3-KD group had significant reductions in fibrosis-related genes (all P<0.05) and a tendency of reduction in collagen fiber area (P>0.05). Conclusion NLRP3 knockdown can significantly improve hepatic fat deposition and inflammation in a mouse model of HFHC-induced NASH. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of extracellular matrix, which leads to the accumulation of interstitial collagen and other matrix components. Matrix metalloproteinases ( MMPs) and their specific inhibitors, i.e., tissue inhibitors of metalloproteinases ( TIMPs), play a crucial role in collagen synthesis and lysis. Through a literature review, this article reviews the experimental studies of liver fibrosis based on MMPs/ TIMPs, summarizes the components that may exert an anti - liver fibrosis effect by affecting the expression or activity of MMPs/TIMPs, and attempts to clarify the mechanism of MMPs/TIMPs in regulating collagen homeostasis, so as to provide support for the development of anti - liver fibrosis drugs. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Intrahepatic cholestasis (IHC) is a dysfunction of bile production, secretion, and excretion caused by various factors including genetics, immunity, inflammation, stones, and tumors, and therefore, the bile is not normally discharged into the duodenum and reversely flows into blood, which causes a series of clinical diseases with organic damage, metabolic disorders, and dysfunction. In recent years, with the deepening of clinical and basic research, intestinal microecology is found to play an important role in the development and progression of liver diseases. This article reviews the mechanism of action of intestinal microecology and inflammatory factors in intrahepatic cholestasis and explores the research advances in the role of probiotics in regulating intestinal flora stability and improving intestinal microenvironment, so as to provide a basis for clinical treatment, scientific research, and drug research and development. [ABSTRACT FROM AUTHOR]